Whiteside v. Parvizi: Intra-Articular Antibiotic Irrigation Has a Role in Revision Arthroplasty
OTW Staff • Tue, September 26th, 2017
This week’s Orthopaedic Crossfire® debate was part of the 17th Annual Current Concepts in Joint Replacement® (CCJR) - Spring meeting, which took place in Las Vegas. This week’s topic is “Intra-Articular Antibiotic Irrigation has a Role in Revision Arthroplasty.” For is Leo A. Whiteside, M.D., Missouri Bone & Joint Center, St. Louis, Missouri. Opposing is Javad Parvizi, M.D., F.R.C.S., Rothman Institute, Philadelphia, Pennsylvania. Moderating is Andrew J. Shimmin, M.B., F.R.A.C.S., Melbourne Orthopaedic Group, Melbourne, Australia.
Dr. Whiteside: The literature, the science and the surgical principles strongly favor direct topical antibiotics in surgical wounds with clean implants. While it may not deserve further thought, it does require some teaching because I have a professor, Professor Parvizi, that I’ve got to teach.
It ain’t easy to teach a professor, but I am going to share the recipe.
Vancomycin and polymyxin—it’s the gram negative and the gram positive. You do it in large concentrations—1,000 micrograms per liter, 250,000 units per liter, respectively – to be started immediately and continued throughout the procedure.
Intravenous vancomycin gives you 5 micrograms per milliliter compared to 1,000. It makes a difference in the killing power of the antibiotic. You irrigate throughout the procedure for an hour or so, then you stop and the antibiotic concentration tapers off for about 12 hours.
It’s more effective to irrigate with a pumped device/pulsatile lavage. Bulb syringes are not quite as effective. Irrigate the medullary canals in the femur. Continue throughout the procedure washing the debris out and continuing to pump antibiotic irrigation fluids into the soft tissues so it remains as a depot. Fill the medullary canals with antibiotic irrigation solution. Then also pump it into the soft tissues as you close. Close the tissue firmly and it still leaks a little bit of antibiotics out through the wound.
The literature, as I said, is compelling.
Lord in ’83, with intra-articular antibiotics in vascular surgery, the infection rate went from 5% to 0.1%.
Bob Volz (1984), friend of mine, found that tissue levels in bone tendon muscle subcutaneous tissues are bactericidal and remain high for 24 hours. Zebala (2014), put a plate on a rabbit tibia, contaminated it and then irrigated half of them with antibiotic irrigation solution. Came back in a week and sacrificed. Lo and behold, the ones that had been treated with antibiotics had NO bacteria and 39 of the 40 untreated DID have bacteria!
Strom (2013) in the neurosurgical literature found that Vancomycin powder at the end of the case decreased the infection rate in instrumented spinal cases from 11% to 0%, highly statistically significant. Myung (2014), adolescent, thoracolumbar fusions, retrospective study—11% to 0.7%, highly statistically significant. O’Neil (2011) retrospective posterior spine fusion surgery, large group—13% versus 0%.
Godi (2013) found the infection rate in a prospective randomized controlled study - 13% without antibiotics versus 0% with antibiotics. When he looked at the cost savings he found that for every 100 cases about half a million dollars was saved. That’s well worth the cost of the antibiotics, I’ll tell you.
My personal experience over 2,000 cases, over a 10-year period of time, no infections. I had some wound problems, but I had no acute infections. And there are other people like Dick Scott who report the same thing.
Now, Jay, don’t tell me about Betadine. Betadine in a wound is not the same. It’s toxic to epithelial cells. It’s toxic to osteoblasts and that goes on for weeks after surgery and it’s toxic to chondrocytes, marked reduction. So that is not the answer. The answer is straightforward. It’s in your operating room. It should be in your hands. Antibiotics, directly in the wound, throughout the entire operative procedure.
Dr. Parvizi: Thank you, Leo, for your very enlightening talk. Leo just managed, however, to skip the actual point in this debate.
We all recognize that periprosthetic joint infection is a real devastating complication that leads to terrible morbidity and, in fact, it’s worse than many cancers in terms of its mortality. So making efforts to try to prevent infection is certainly worthwhile.
So let’s share some facts.
Despite all our efforts we cannot have an absolutely sterile incision. Prevention of SSI [surgical site infection] is a multi-step effort and not just a simple one-step procedure. That’s why a lot of the organizations including the Infectious Disease Society of North America have produced guidelines. As you know the CDC [Centers for Disease Control and Prevention] guidelines are about to be published. They’re going through the final throes of evaluation by the government. It will be out very shortly.
So how do you get SSI?
- Patient’s skin and organ flora.
- Contamination through gloves, instruments, etc.
- Droplets through the air.
- People in the operating room.
We need to make efforts to try to reduce skin flora contamination and that can be done either by bath or shower, chlorhexidine, etc. CDC guidelines that will come out advise the patients to shower or bath, full body, with either soap or antiseptic agents at least the night before the operative day. Please remember that CDC guidelines will set policy moving forward. We all probably need to start to think about implementing this into our practices in the future.
People in the operating room. Ten thousand bacteria per minute, per person in the operating room. Do the math. Huge number of bacteria in the operating room and people shouldn’t be in the operating room unless they belong there.
Intraoperative irrigation solution…it’s almost asking if you need to wash your hands after going to the bathroom. The answer is yes, of course we need irrigation solution.
Does it need to be antibiotic solution? No, it doesn’t and I’ll tell you why. Cost effectiveness. The cost is not negligible. Efficacy, you’ve just seen some papers presented by Leo…I will urge you to go back and read those papers. There’s never a control arm. Efficacy is minimal and most states, in fact, are against use of antibiotic impregnated solution.
Fantastic work done by Jeffrey Anglen shows that the three different solutions: saline, saline antibiotic solution that did include neomycin and polymyxin versus liquid soap. They found an antibiotic had no significant effect on bacteria removal compared to saline alone. So I will argue that most of the data that Leo just presented to you has to do with irrigation itself and nothing to do with the addition of antibiotics.
Another study by Jeff, 458 open fractures, bacitracin versus soap, and what he found was in fact there was no additional benefit to use of the antibiotic over soap in this open fracture model.
We need to exercise antibiotic stewardship. If you don’t know about AMR [antimicrobial resistance] I urge you to read up on it. In fact, what we’re going to see approximately 50,000 deaths per year as a result of antimicrobial resistant organisms. If we don’t get our arms around this issue by year 2050, we’ll see more people die of AMR than cancer.
Unfortunately the use of antibiotics increased by 40% between year 2000 and 2010, and at this point AMR appears to be a very, very important issue.
So what do we do? In the absence of data I continue to use dilute Betadine with very, very low infection rate in my group. And two other issues—allergy is an issue especially if it is unrecognized. We had a patient who died of allergy to bacitracin last year at my institution as a result of unrecognized allergy.
Toxicity, sure. Dilute Betadine is toxic, but so are antibiotics. There are numerous studies published that show antibiotics also have adverse effects on chondrocytes and osteoblasts and fibroblasts.
So in the absence of data, I think we all need to get to work and generate the data before we stand up here and advocate for things that lack proper data.
Moderator Shimmin: Interesting subject. I have a question for Jay. Is there not just a little bit of you that kind of likes the idea of having some local antibiotics on first principle?
Dr. Parvizi: I think you need to have an antimicrobial agent in the incision because of the presence of bacteria. And in my opinion dilute Betadine is more antibacterial than vancomycin.
Moderator Shimmin: You’ve been pretty clear on that.
Dr. Parvizi: I’m not pretty clear. The literature is. There are 10 randomized prospective studies, the CDC feels that there is enough data to make that recommendation. They make a recommendation against what Leo is standing out here to propose.
Moderator Shimmin: The spine surgeons come to different conclusions. Can we not see any synergy there?
Dr. Parvizi: They don’t. If you actually look at the spine data in a couple of the papers that Leo has just cited here, they are very weak. They’re actually implemented from a multi-step strategy as opposed to single step and spine infections are a little different from periprosthetic joint infection. All I argue is what Leo is seeing is part of a multi-step effort that he as a very careful surgeon has implemented and if he removed the antibiotics from the solution and instead added dilute Betadine, perhaps he’d see exactly the same effect.
Moderator Shimmin: Maybe you’re just not happy doing this, but a lot of people will put antibiotic in the cement.
Dr. Parvizi: Okay, so antibiotic impregnated cement in itself is a very, very important debate. The Australian Registry, right now, shows there is absolutely no difference between the use of antibiotic impregnated cement versus no cement. And if you believe the New Zealand Registry, the March paper that just came out in The Bone and Joint Journal shows that the use of antibiotic impregnated cement increases the incidence of infection.
Moderator Shimmin: In a revision setting for infection, will you put antibiotic into cement for a spacer or something like that? Do we see any synergy there? Or are you still firm that there’s still no role for any local antibiotic?
Dr. Parvizi: No, I think in the infection setting, the infection rate is higher, you might be justified in thinking about adding it to the cement spacer and even in the high risk patients the benefits might outweigh the risks. In that patient population.
Moderator Shimmin: Leo, in this era of evidence-based medicine, can we really justify this when there is such little evidence in the arthroplasty fields?
Dr. Whiteside: The evidence is overwhelmingly in the favor of using antibiotic irrigation. I just presented about 10 studies. Controlled studies that showed clearly that in clean orthopedic surgery with implants, the infection rate is decreased by a factor of 10 or more. And that’s in arthroplasty as well as spine. How many more studies do we have to do? We quoted this one study that shows that when you irrigate in vitro a staph that’s already laid down as biofilm, already created its slime, that antibiotics are ineffective. And that’s true if you want to overcome bacteria that are already in a biofilm, you gotta go over 1,000 times greater than minimally inhibitory concentratration to eliminate that with antibiotics. You can do it, but you can prevent that slime from forming with ten times over minimally inhibitory concentration. That is why you irrigate them early and often. Just like they vote in Chicago—early and often.
Moderator Shimmin: He’s not budging. I can’t get him to budge.
Dr. Parvizi: Let me ask Leo one question…can I? What was your infection rate prior to the use of irrigation solution? Antibiotics?
Dr. Whiteside: I can’t give you that because I was taught to use antibiotic irrigation when I was in residency by a field surgeon from the U.S. Army. So I used antibiotics throughout my career. I use the current technique over that ten year period of time that I quoted. It was very low before that, before these ten years.
Dr. Parvizi: So you think it made a difference?
Dr. Whiteside: I think my use of antibiotic irrigation solution in clean orthopedic surgery has made my life so much better. I can go ten years and I can tell my patients, your chances of getting an infection in my hands are less than 1 in 1,000. It could happen to you, but it’s going to be much more related to you and your weight and that sort of thing, rather than the clean surgery.
Moderator Shimmin: A question from Dr. Lombardi.
Dr. Lombardi: Jay, you’re advising us to use Betadine. So I just get the bottle off the wall in the cabinet and pour it in…why don’t you give us some instruction on what we…
Dr. Parvizi: No, unfortunately the Betadine needs to be sterile and it needs to come from sterile packets. The best ones that we use are the ones that are in urinary catheters. The aluminum foil that has about 20cc, you add about 500cc of saline. Pour it in for three minutes, leave it in there, but then wash it out. Leo is right. Betadine is cytotoxic and if you leave it behind you could affect fibroblasts.
Dr. Whiteside: Before you start using Betadine, please read the three studies that I quoted.
Moderator Shimmin: Gentlemen, we do have to stop. We thank these guys very much.
Please visit www.CCJR.com 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.