Christopher K Bromley, DPM presents the physiology of wound healing and the importance of oxygen in that process. Dr Bromley reviews the role of compression in the healing of venous stasis ulcers as well as differentiating topical versus chamber oxygen therapy.
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TAPE STARTS – [00:00]
Harold: Our next speaker has been a great friend to the Superbones meetings and the Residency Summit meetings. It's Dr. Chris Bromley. Dr. Bromley practices in this major metropolis called Poughkeepsie, New York. You can't find it on the map but it is there. Dr. Bromley is currently the Department Chair of Foot and Ankle Surgery at Vassar Medical Center. And interestingly, he has always had an interest in nutrition, along with other factors, in the healing of wounds. And today, Dr. Bromley is going to share some thoughts on topical oxygen. So please, welcome my good friend, Dr. Bromley.
Dr. Chris Bromley: Good morning. Thank you, Harold, for the introduction. And having had a few meals with you, you are well-nourished and in great shape for a man of your stature. All right. So in the time that we have allotted, I just wanted to thank Dr. Collins for – it was a great lecture, and I think I really wish she was around when I was helping run a wound care center, because I kept telling them, "It's all about nutrition." And they kept looking at me like, "No, it's all about the hyperbaric. It's all about the hyperbaric." But it's definitely the more we look at our patients as the whole package, you know, and even the lecture we talked this morning about and heard about edema, and how important that is, and I'll give a little talk about that tomorrow.
I don't know about the MIPS lecture. That was like attending statistics at 7:00 a.m. when I was an undergrad. It was painful but very informative. So thank you, Dr. Lederman. All right. So moving forward. We're going to talk – shift gears a little bit. We're going to talk about the use of topical oxygen and sort of how it integrates the oxygen, as well as the compression in a moist wound environment. So from a disclosure perspective, I speak for a number of companies. I do lecture for the sponsor today. From an objective perspective, we're going to talk about and understand the role of oxygen and wound healing. We're going to review how you can incorporate compression with wound healing with topical oxygen, and then differentiate between the benefits of topical versus a hyperbaric chamber.
My experience with hyperbaric chambers was I always – as part of the wound care center, thought that they were very effective way of offloading the patient five days a week for two hours, and it was very effective for us. But there's obviously some cost and coverage considerations moving forward. So in order to get wounds to heal completely, we have to look at all the different factors, the things that we talked about this morning about nutrition. We have to look at what is available for us. Now, when I was in the wound care center setting a number of years ago, topical oxygen was relatively new. They were small devices. They were just pumping into the wound dressing. I didn't find that particularly effective.
Topical oxygen has evolved significantly. The devices are reusable. They're portable. They can go out to the patient's home. The patient doesn't have to worry about coming to the center. It's going to use a disposable chamber that is going to incorporate very high levels of tissue oxygen and a graduated compression. As you heard in Dr. Lederman's lecture this morning, getting rid of the edema is extremely important and we've done a very poor job. I will admit to you that as a lecturer for many years on peripheral arterial disease, I really missed the boat on lower extremity edema.
If we're not evaluating patients and understanding the role of lower extremity edema, and we'll talk about that in-depth tomorrow, we're sort of missing the boat. It doesn't matter if a patient has a pulse. It's great, but if they've got venous hypertension and lots of edema on the return side, your oxygenated blood is not able to get into the wound. If it's not able to get into the wound, you're not delivering the nutrition that the wound needs. You're not delivering the oxygen and it's not going to heal. So using a device such as the topical oxygen that incorporates compression, that will help heal the wound much, much faster.
We can also incorporate some moisture into this environment and that will keep our wounds from drying out. So typically, what we're looking to do is use these cylinders. We're going to get graduated compression. We're going to get better wound healing. There are no complications, none of the contraindications that we had in hyperbaric chambers, and we can use it for diabetic. We can use it for venous and pressure ulcers. We can also use it post-surgery. That's the way we use some of the other devices we've had. In New York where I practice, it's covered by Medicare and some of the private insurances. Later on, hopefully near the end of 2018, we'll also have Medicare coverage. They're working on that and that will be huge in reference to access for our patients.
So to understand the wound healing process and some of this you know, but just as a reminder, if we look at wounds, wound healing is all about the interaction between the platelets and neutrophils, and macrophages. And overtime, the collagen and wound strength really depends on how effective these are. If we don't have the right nutrition, if we don't have the right tissue oxygenation, then we can't get the healing quality that we're looking for. And what we're going to talk about in the lecture is not only getting the wound healed, but keeping it healed.
So we look at a patient who comes in with a chronic wound like some of the things we've talked about this morning. We understand we've got to look at what happened, what kind of local wound care. Obviously, topical oxygen is great, but it's no substitute to good wound care. The good wound care principle is that we, in podiatry are so good at, that removing the bioburden, doing good surgical debridement, patient compliance, and what we want to do is control these things, and then add oxygenation to get the wound to heal, and get it to heal faster, and more efficiently and also save money.
Because like we talked about in the MIPS lecture, we're going to be paid on compliance. We also know you've all heard about – you know, the not being paid for readmissions. If you're not involved with your hospital, you're going to find out pretty quickly that if your diabetic wounds or your venous stasis wounds keep coming back in the hospital, your hospital is going to come down on you, and they're going to find something else for you to do.
So if we look at chronic wounds, what is the difference in what's going on? We know we look at the [Dowd 06:25] study, we can see that in venous wounds, we've got a lot of anaerobes, and these are one of the reasons it's very difficult heal. We can see the mix bag in a diabetic and then in the pressure ulcers, which usually happen to have more aerobe. So what we're looking at is the different types of microbiome and we're looking at what's going on. And we know that oxygen is one of the best antibiotics we have. So how can we deliver that to the area?
When we look at the chronic wound, we see that there's a huge lack of oxygen due to the poor vascular structure, sort of like we talked about before. If they've got a pulse but they've got the venous edema, we're not getting the tissue oxygenation to that wound. If there's no tissue oxygenation there, then the bacteria takes over. The leukocytes and the platelets, and the macrophages can't do their job. If we give more oxygen, we can help the leukocytes function better and we can get the synthesis of collagen and get the ECM matrix and the revascularization that we need for a quality heal.
We look at this diagram of the wound, we can see in the center of the wound, the oxygen level is very low. Most of the time it's less than 10 millimeters of mercury at the center. We can see as we move closer, we might get closer to 60. But overall, we're not getting the oxygen to where we need it. We need granulation tissue. We need the leukocytes. We need the collagen to form, and if we don't have oxygen there, we're not going to be able to get the wound to heal, and we're not going to be able to get the good quality healing that we're looking for.
So if we look at tissue oxygen levels as we mentioned, the antimicrobial enzymes are very susceptible. And when the oxygen levels are low, we can increase the oxygen level at the center of the wound. We're going to be able to get the function that we need. So what are our options? When I was working in the wound care center, this is all we had. We've got 2,500 millibars of pressure. I don't know about you, I had patients who had difficulty with barotrauma. I had one patient who lost his vision. But in order for this to be effective, the patient has to have intact good blood flow and no venous restriction. Most of my patients had all kinds of arterial and venous disease. So although this was effective, it takes a long time and it's very expensive, and there are number of complications.
If we start looking at topical oxygen and we deliver it, and when we cycle between five and 50 millibars, and we do this with the chamber, we're going to get a much better result because we've got this sequential compression. We've got tissue oxygenation where we need it to be. It's very easy to be compliant. It can be done in the patient's home and it's very inexpensive. This is one of the studies that shows the difference because a lot of times when you start talking about topical oxygen, people are like, "That doesn't work. It's got to be in a chamber." Well, this is a study looking at the local oxygen tension. In this, they've got a non-permeable dressing right over top of this wound, and then this one has a permeable. And you can see that the oxygen tension in the permeable versus the non-permeable.
So this is one of those studies showing you how quickly it will heal with topical oxygen versus when we did the control. This is a pig model showing a full thickness. How much of that oxygen actually gets down into the wound? So in this particular model, the pig has been fitted with a two-millimeter depth oxygen sensor and we can see that the central oxygen tension has increased from five to seven. Remember I told you how low it was, greater than 40, in four minutes. Not only that you get to that higher level, but it stays there even when you're done with the treatment. So we not only see the topical effect but we can also see into the wound itself a much better oxygen sensation than you were getting from the intrinsic blood flow.
So does the topical oxygen defuse through the tissue of the wounds in humans? So if we look at this study, we can see the chamber and we can see pre-treatment oxygen levels are very low. And in these cases, you can see the post-treatment levels are up much higher than where they were and much more effective. And you can see in this particular patient, this is a wound that lots of us are fighting with this diabetic ulcer. It was debrided. And with the oxygenation, you could see a nice beefy granular wound that we're going to be able to get to close.
So this is the slide that we kind of took a look at earlier but you can see topical oxygen provides 800 millimeters of mercury or partial oxygen pressure for diffusion for the maximum enzyme effectiveness in the wound. And there, we're going to see the ATP synthesis go up high. An ATP is obviously the key that's going to drive the collagen synthesis, as well as help with the antimicrobial enzymes, to be much more effective. So the oxygen is obviously the key.
So what happens with the neovascularization? Because we know that neovascularization is important, we can see that in the pig model, the increase of the VEGF expression in the wound, and we can see in the control versus the follow up, you can see the significant expression 20-fold greater. And then, you can see here a significant improvement. So this is stained smooth muscle assay with seven millimeter punch biopsy. Seven days later on this study, you can see significant improvement with the topical oxygen. So what happens to our tissue?
Well, we want these wounds to heal, but we want them to stay healed. So one of the effects of topical oxygen is that we can see that we have significant improvement and much more defined epidermis compared to the control side. So you can see, this looks like what epidermis should look like versus this sort of very random pattern here, and this is one of the reasons why not only do we see advanced healing with topical oxygen, but these patients come back, you know, 12, 24, 36 months, and we're not having the reoccurrence that we'd seen with other modalities. So you can see in this, you know, the H&E stain in the granular tissue, you know, this is very normal versus very random. So you can see much better advanced, much better quality than in the control group.
So the way I use this modality is the oxygen is cycled between 10 and 50 millibars within the chamber around the leg. It's a higher tissue gradient and you're going to get a five-fold increase in PO2 compared to what would normally be there, and the lowest pressure is optimal. If you get higher than 50, just like we talked about in the compression lecture, that starts to be occluding to the arterial flow. So the 10 to 50 is ideal. You don't really want to be any higher than 50, and then the second effect is the sequential compression. When we talked about the edema and interstitial space, we know that our wounds aren't going to heal if we have venous hypertension.
So you're going to get that sequential compression from distal to proximal on the leg that's going to get rid of that edema and that pulsing effect drives the arterial and venous interaction within the wound. So that's very, very important and that's a huge part of the wound. Now, if you have a wound that – you know, and wounds can't be too dry. If they're dry, they're like a desert. They're not going to granulate. So we can add humidification through the wound and we can also add antibiotics to that humidification to help fight off any infection.
These are all the studies that have been done. You and I are too far away from this to actually read it, but just to give you an idea, there's lots of literature out there dating back to the '60s as to the effectiveness of topical oxygen. This is one of the studies, a little bit easy to read. It's got 1B evidence rating about how effective it is, and very, very safe. So this is some of the studies broken down looking at patients. You can see in this particular study looking at 132 patients with venous ulcers showing a 90% reduction in the wound. The next study is 40 patients and diabetics, again, 90% healed. In 12 weeks, the venous ulcers were 50% healed at 12. Again, these are very good. Most of these venous ulcers had been present as from Dr. Lederman's lectures, you know, greater than nine months.
Another diabetic study showing 80% healing, again, in their follow up study for venous leg, 80%, so very, very strong, you know, 80% to 90% heal rates with topical oxygen within that 12-week period, which is huge. Here is a case. This patient had a venous leg wound for greater than nine years. You can see the pretreatment. After eight weeks of treatment, you can see a significant improvement. And again, what we're seeing here is a wound that's healed, but it's a good quality heal, so that we can prevent reoccurrence. It is no substitute to using the compression garments that Dr. Lederman talked about for follow up.
Once you get this healed, you do have to follow up with the patient because obviously their venous disease didn't just magically disappear, but you can imagine that the quality of life that this patient is going to have, is significantly better. Looking at some technical and clinical outcomes in topical oxygen, again, this is 132 patients, 67 were managed with topical, 65 were managed with conventional compression dressing. Looking at the results, 96% of the patients healed with topical versus 61% with compression only. And again, after 36 months, 47% of the healed with conventional had reoccurrence. Only 6% of those that we use topical oxygen with a compression sleeve had reoccurrence. So that's a huge improvement, overall quality.
All right. So here are some pictures of that wound that we showed you, showed you the progression, you know, how it's improving, and you can see at three weeks that looks much better, four weeks, six, seven, and that's obviously a great outcome. All right. So we looked at some diabetic wounds. Patient was referred for amputation. This is pretreatment and then this is 10 weeks later. That's a foot that you can walk on. And obviously, significant improvement with topical oxygen versus if the patient had had amputation. Looking at topical oxygen for severe diabetic foot, this is the Blackman study looking at 28 outpatients. They had a 60-minute session five days a week with standard of care patient. The standard of care was just a silver dressing. So these patients had 82% heal versus 42% at 90 days, so significant improvement with the patients with topical oxygen over standard of care alone.
This, as you can, is just a close-up picture of that wound we talked about before. You can see it at three weeks, I'd show you some of the progression. What is the effectiveness on diabetic ulcers versus some of the conventional therapy? So if you look at the studies from Armstrong and Bloom, you can see that the VAC with standard of care for DFU's healing is typically between 43% and 56%. If we look at various wounds with topical oxygen, again, three studies that we referred to, we see 82% to 92% healed rate, so significant improvement of topical oxygen therapy.
All right. Large random clinical study, multinational study. This is going on 220 severely infected diabetic foot. Twenty studies between here and Europe looking at primary outcomes at 12 weeks' time to closure. Obviously, this is still going on. So what are the different topical oxygen devices out there? When topical oxygen first came out, I've had experience with most of these. They were pumping oxygen but there's no compression, and there's nothing dealing with the leg edema. This particular device is available. The downside of this particular device is it's only 22. And as you heard earlier today, 22 is not enough and it's constant. It doesn't replicate the body's natural pumping mechanism which is what we're looking for to help.
When we cycle with this particular device between five and 50, or 10 and 50, we can see that we get the oxygen tissue levels that we're looking for, and we're getting rid of the leg edema and that's helping us overall. So we're going to be able to affect the patient a much better quality heal. So we're looking at other modalities. Topical oxygen works well with all of the other dressing that you have at your disposal. The only thing we don't use it with is over a VAC and that makes sense because obviously the VAC has an occlusive dressing.
There are colleagues that I have that are using the VAC and they'll take the VAC off for a VAC holiday for two or three, to four days, and then go and use the topical oxygen, and then go back to using the VAC. So you can alternate the VAC with topical oxygen. But as I said, unlike the chamber that we were using in the wound care center, we had to be very careful what dressings were used. With topical oxygen, you don't have to worry about it at all. So it's very symbiotic with all the biologics that we have.
Here are some cases looking at mesenchymal stem cell substitute in conjunction with topical oxygen. You can see patient here had TMA. They had some – obviously, there's some breakdown, so that we went ahead, and you can see a graphics applied to the wound, staged, put in place, and then using the topical oxygen to increase the healing. This is a patient who is a smoker and quite a difficult case. You can see the wound as it progresses while out significant improvements in these two particular cases.
Clinical evidence, topical oxygen compared to full body. Again, we talked about the difference in the risk and complications, and there's a significant cost obviously over chambered HBO over topical, and that doesn't even include, or all the consultation and transportation cost getting the patient to the wound care center. Let's look at topical oxygen versus control groups. Topical oxygen is statistically better for healing overall. The average is 80% healed within 12 weeks and there're no contraindications at all and no adverse events in any of these studies.
Some other cases looking at full, this is a case where we compare two almost identical wound. So this a patient who's had first rate significant debridement where it's going to do a chambered HBO versus topical. You can see both wounds are progressing. Now, the healing time in the HBO patient was slightly shorter than the topical. The difference in cost was significant.
So this patient was able to stay home and they had a good outcome with minimal cost versus significant cost for HBO, and obviously without the risk and complications of HBO. So again, this is showing you the study results versus control group. This is exactly what it looks like in the home environment. You got an oxygen generator. They're not required to have any oxygen tanks. There's a device that will generate the oxygen and then it's pumped in through the chamber. It maintains the ideal moist wound environment.
It will suppress the bacterial growth because of the oxygen wound tension. It will increase leukocyte antimicrobial, which will help fight off, stimulate new capillary growth like we showed you in the slides with the VGF, increase collagen, and increase tissue strength, and will stimulate the peripheral circulation, and get rid of that lower extremity edema, which we've seen as a significant factor. So these are some of the references. These are all available in the presentation. We will hopefully have it up online for you, so thank you very much.
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