BTK_inhalinjury_090724

Welcome to another episode of Behind the Knife. On today's burn section, we have the burn inhalation injury podcast with your moderators, Tommy Tran. I'm a burn and surgical critical care fellow at the Arizona Burn Center. This is Kiran Diamanahalli. I'm a critical care and burn fellow at Mass General Hospital.

Excited to be here. Your guests today are Kevin Foster from Arizona Burn Center, Tina Palmieri from EC Davis, and Ryan Rihani from the UT Houston Burn Center. Dr. Rihani, what is burn inhalation injury? 1st of all, thank you guys for having me. I'm honored to be here with such other esteemed guests in our institution.

We define burn inhalation injury as damage to the respiratory tract that results from the inhalation of hot gases, smoke, chemical fumes that occurred during a fire or some other incident involving intense heat. These injuries often occur in addition

to the external burns that we're all so aware of, and they affect both the upper and the lower airways in different mechanisms.

So, when a fire burns, we often see the smoke that results from it. And the smoke is a complex mixture of gases and particles that are harmful to the respiratory system. They contain carbon monoxide, cyanide, hydrogen, particulate matters, and various irritants that can damage and significantly alter the respiratory tract.

And it starts in the nose, works its way all the way down to the bronchi and the alveoli. Okay, why is it so important? You know, if you look at the National Burn Repository, smoke inhalation injury is present in about 10 to 20 percent of all burning admissions. And why is it important? Well, it significantly increases morbidity and mortality in these patients.

Pneumonia and ARDS are really the primary drivers of that increased mortality. The risk really scales with the cutaneous burn. So the incidence of smoke inhalation injury increases

from less than 10 percent in patients with a mean TBSA of about 5 percent to more than 80 percent in patients with a mean TBSA of 85 percent or more.

Let's go through some scenarios, Dr. Riani. A patient comes in from a July 4th barbecue, a outdoor propane tank explodes in his face and he comes in with facial burns. Are you concerned for inhalation injury? Great question, Tommy. You know, we see quite a few of these in Houston. A lot of people love barbecuing out in the 100 degree weather.

At this point, I would say maybe, but err on the side of no, I'm not particularly concerned. Second scenario. A patient comes in after an MVC rollover resulting in a fire with a prolonged extrication. I am absolutely concerned. The third scenario. The patient comes in with facial burns while smoking on supplemental oxygen.

Not particularly concerned.

And last scenario. A patient comes in after rescuing pets from a house fire with no obvious burns on the face but with soot in the nostrils. Yes, I'm concerned. What about these scenarios tell you that you are concerned or not for burn inhalation injuries? You know, the primary thing that I look at when I'm evaluating these patients after we get called to the emergency room is their exposure time to smoke, as well as whether the smoke inhalation or fire exposure happened in an enclosed space.

Enclosed spaces increase the risk for prolonged time in the fire, prolonged exposure to the smoke inhalation. So when you're talking about an outdoor propane tank explosion with facial burns, I'm not particularly concerned. That doesn't mean that I don't evaluate them and I don't go through their nasal fiber optics and take a look at their nasopharynx and oropharynx, which can

definitely be involved from the thermal injury itself, but for injury to have occurred deeper and be defined as inhalation injury, I wouldn't be quite so worried.

Now when we're talking about a rollover MVC or somebody going back into a house fire to rescue pets, you are looking at prolonged time and exposure to that smoke. And with that prolonged exposure comes a host of irritants that will extend past the nasopharynx, past the oropharynx, Nearly impossible to run back into a fire or sit in a car or holding your breath for an extended period of time.

So, you will have, at some point, exposed your alveoli and your bronchi to the irritants of the smoke. And therefore, the resultant inhalation injury won't be obvious at first, but will show itself in the next 6, 12, 24 hours. Regarding facial burns while smoking on supplemental oxygen. We get too many patients that come to our unit intubated because in the emergency department, they've got

soot in their airways or they've got syne nasal hairs some sort of oral mucosal swelling.

But in most of the scenarios, I find that these patients are extubated not only quickly, but even sometimes in the same day. These are patients that are at high risk for doing poorly on the ventilator. They have underlying pulmonary disease, and when they do get facial burns as a result of this oxygen setting on fire while smoking, the fire and the thermal injury itself does not extend past the nasopharynx.

And when we do our nasal fiber optics, we see that most of the time the vocal cords are not swollen and almost every single time there is no underlying inhalation injury. So, you know, how do we diagnose inhalation injury? We kind of alluded to some of this already. Really one of the principles is to maintain a high index of dissipation.

Airway compromise from edema, bronchospasm, mucous plugging, or cast formation can occur over a broad timeline, you know, minutes to days,

even after the injury. The circumstances really come into effect here. So, burns in closed spaces, loss of consciousness, disability, extremes of age, so the very young, the very old, and prolonged excavation times, it can all increase the risk of inhalation injury.

We think about both soft signs and hard signs. So, soft signs would be, you know, things like singed nasal hairs, burns to the face or neck, nausea, vomiting, black carbonaceous debris or sputum, and increased work of breathing. And hard signs, kind of more reliable signs, would be reduced oxygen saturation, cyanosis.

Strider, visible mucosal changes in the upper airway. So those are all things we look for. Of course, we measure serum carboxyhemoglobin levels. At normal levels are less than 2 percent in non smokers at least, and maybe less than 3 to 5 percent in smokers. There are kind of characteristic CT chest findings, although not very specific to smoke inhalation injury.

Things like interstitial markings, ground glass capacities, areas of consolidation, and bronchial wall

thickening. You can order pulmonary function tests, radionuclide imaging with 133 xenon. You know, other than the measuring serum carboxyhemoglobin, the latter three really aren't in kind of routine clinical use.

We don't order those tests unless we have a specific question in mind. Tommy, what would you say is a gold standard for diagnosis of smoke inhalation injury? Definitely for Kosciutki. Grade 0 is no injury. Grade 1 is mild, where there is minor or patchy areas of erythema deposits in the proximal or distal bronchi.

Grade 2 is moderate injury, where they have moderate degrees of erythema, deposits, bronchorrhea, or bronchial obstruction. Grade 3 is severe injury, where they have severe inflammation, friable, mucosa, copious deposits, bronchorrhea, or obstruction. And then Grade 4, evidence of mucous clotting, necrosis, and illuminal obliteration.

And once we see the photo

It likely won't leave your mind. Remember that there are limitations with bronchoscopy. And sometimes we cannot evaluate to just a lower respiratory tract. Sometimes it fails to account for the heterogeneity of the inflammatory response between individuals. And we need repeated bronchoscopies to assess for the evolution of inhalation injuries.

Dr. Riani, could you talk about your bird inhalation protocol? Absolutely. So, you touched a little bit on it there with your repeat bronchoscopy to assess evolution, response to therapy. You know, we do our daily broncs, not necessarily diagnostic only, but also therapeutic. A lot of these patients develop soot related problems.

secretions and these secretions can become a little too much for the patient to handle on their own. Our daily bronchoscopies are focused not only on regrading but also to help the patient in their clearance of a lot

of the soot. This works especially well in patients who are on conventional modes of ventilation where the ventilation is not necessarily aimed at helping them clear the secretions but simply providing ventilation and oxygenation to the patient.

Then we move on a little bit into reassessing our therapy. Once we've taken our daily bronchoscopies into account, we've seen the evolution of the inhalation injury over time. We get a better idea of when it's appropriate to stop our ongoing nebulized therapies. And we'll get a little bit more into that later.

The overall goal is not just diagnostic, but also therapeutic and helping and guiding our therapies in the future. Karen, let's take a moment and trade our bronchoscopes for goggles and mass spectrometers and try to understand the chemistry behind burn and elation injuries. Could you fill us in? Happy to.

Smoke is really a colloidal product of combustion. That's a mixture of gases and air sliced solid and

liquid particles, and the composition really depends on the specific combustible material that are involved in the fire. So high temperature fires in oxygen rich environments burn cleanly, so they produce less smoke and mostly carbon and oxygen oxides.

If there's less oxygen, there's incomplete combustion, and that really leads to a greater diversity of compounds, things like ammonia and hydrogen cyanide. The list is really too extensive to kind of go over in this setting. I'll say that carbon monoxide and hydrogen cyanide likely have the greatest impact on mortality.

Wow, that's fascinating. Okay, let's zoom back out to the alveolar level. Could you tell us about the mechanism of injury, especially on the upper airway versus lower airway? Sure. So direct thermal injury really affects nasal cavity and oropharyngeal mucosa, the region of the airway that has efficient heat exchange.

Injuries below the vocal cords are less common from heat. The exception to that of course, and there is an exception to all rules, is exposure to large volumes of steam or superheated vapors

in industrial settings. That can lead to severe chronic edema. Chemical injury by particular deposition depends on the size and solubility of the particles themselves.

So particles greater than five microns rarely pass through the vocal cords due to entrapment in mucoid secretions, as well as a robust ciliary clearance in the nasopharynx. And the exception to that rule is in the setting of fire and smoke, damaged cilia and mouth breathing due to laser pharyngeal irritation can lead to large particles being sent down as lower airways.

That makes a lot of sense because with the nasal pharynx and the oral pharynx in normal physiology working as heat exchange, thermal injuries normally would stop at the upper airways. Whereas smaller chemicals would bypass them and then make its way down to the lower airways where they would do damage.

Exactly. At the upper airway level, we have protein denaturation, epithelial destruction, complement activation, and release of reactive

oxygen species, histamine, and damage associated molecular patterns. That leads to erythema, edema, bronchorrhea, and ulceration. You have increased worker breathing due to airway resistance and reduced compliance with the airway.

And we also see increased minute ventilation requirements due to hypermetabolism. In the lower airway, you have a release of neuropeptides, vasodilators, and chemotraxins. You have the same cascade involving reactive oxygen species that can combine with nitric oxide to produce reactive nitrogen species.

We also see a modification of key enzymes and lipids that trigger apoptosis pathways, impaired bacterial clearance by airway cilia that can increase the patient's risk of developing pneumonia. And then finally, excess mucus combined with muted airway epithelium and fibrin deposits can lead to those devastating airway casts.

At the alveolar level, you have aleiss secondary to decreased levels of surfactant, a loss of hypoxic pulmonary VAs constriction, which leads to

mismatch between ventilation and perfusion. And then finally, alveo. Hemostasis is effected by decreased lytic activity. All right, I will now hand the raise to and Dr.

Palmer or the remainder of the pathophysiology section. Sounds good. So, Dr. Palmer, you have worked extensively with animal model studying inhalation injury. What commonalities have you observed between those animals and your own patients? Great question. Ultimately, to really study inhalation injury, we have to go to animal models because there's too much variability in what we see clinically.

Different animals breathe very differently and their lungs are very different than humans. Probably the most studied and probably has the most similar long pathophysiology that we can study has been the sheep model and that was championed by Dr. Dan Traber. And basically, inhalation injury accentuates the burn injury.

So, 2 plus 2 no longer equals 4, 2 plus 2 equals 6.

And that's a consistent finding in animal models that inhalation injury portends poorly for survival, so it increases mortality in any situation and also increases lung injury. That's probably one of the biggest things that you see. The second is that animals require increased fluid resuscitation when they have inhalation injury in combination with a burn injury.

And the third is that, just like in humans, you see a higher incidence of pneumonia. in animals who sustain inhalation injury. And very last, most animal models are done with pure smoke, such as pure cotton smoke or pure wood. If you try and mix the chemicals that are currently present in house fires in the United States, it's very difficult to develop a model in which the animal survives.

So even the best animal modeling that we've done to date does not fully replicate the situation in humans. That's fascinating. Thank you. You know, kind of, on the heels of that, and

you know, when we're thinking about long term morbidity from smoke inhalation injury, we're kind of left with population level studies.

But what has been your experience and your thoughts on the long term consequences of smoke inhalation on these patients? The short answer is it's complicated. It depends on what you consider long term, and it depends on what you consider in terms of morbidity. All of the studies are on long term outcomes after inhalation injury have lots of confounders.

For example, some of the best long term studies have been done in coal miners who sustained smoke inhalation injury during fires in the coal mines. It turns out that most of them were also rabid smokers. And so all of the data from that particular population has smoking as a confounder. And we have the same thing in inhalation injury.

When we look at our patients, there's a lot of smoking, alternative substance use, association with concomitant burns makes it difficult to get a

consistent population. Having said all that, Overall, the gestalt in the literature, and there is a paper published, it's really old now, but I think it bears thinking about is that there's a rule of thirds.

About a third of the people who have an inhalation injury have no long term sequelae. A third of the people have progressive lung dysfunction. And about a third of the people have a fixed lung dysfunction after injury, and it's a rough rule. It was published in a small paper many years ago, but as I review my patients who've had an inhalation injury, those with real inhalation injury, bronchoscopic proven, lower airway injury, tend to fall into that 30 30 30 rule.

Now, when you think of the other long term morbidities in terms of psychological sequelae, those are also very real. Because if someone has difficulty with exercise, they have difficulty with socialization because of their inhalation injury or their burn, that is a whole different set of problems

that is almost unexplored in inhalation injury.

Thank you, Dr. Palmieri. You know, I think it is useful to have a rule of thumb when talking to patients and kind of prognosticating. Perfect. So we'll move to the next topic, which is medical management and controversies. So Tommy, I have a question for you. When do you actually intubate these patients? I'll present three patients to you.

The first is a facial burn who was smoking on oxygen. He's doing well, was sitting in the ED for several hours and can be observed for six hours or overnight and I don't think he's going to decompensate. The next patient is on the other side. That patient is intubated coming in. We did bronchoscopy, and we confirmed inhalation injury.

That person will stay intubated, will continue to get resuscitation, and be extubated down the road. Remember, lungs have a large mucous membrane, and we have to properly

resuscitate the patient. For patients who are intubated, we have to ensure that their head of bed is at least 30 degrees. They have proper oral care, subglottic suctioning, we have to minimize sedation, extubate when they meet criteria, and they have early enteral nutrition.

And then the middle patient is the one that can go either way. Can the patient protect their airway? Do I have a concern that the patient will lose their airway? Do they have a reduced level of consciousness or will have a reduced level of consciousness? Thank you for this. And do I think that their face will swell in the coming hours?

If any of these are a yes, then I will intubate them. Yeah, and I think it's useful to think through some of those scenarios because we've received these patients often intubated from the field or intubated prior to transport. And it's difficult, I think, because they're coming from centers that don't have a lot of expertise in dealing with burns.

They have to make a tough call whether to intubate the patient prior to transport. The consequences of losing that airway during a long transportation

time can be catastrophic. There is a well documented over intubation rate. We often excavate these patients following an initial bronchoscopy, hospital day zero, hospital day one, but it's not an easy decision.

You know, we have other therapies that we use, things like inhaled bronchodilators, aerosolized heparin. Eucalyptics like N acetylcysteine they're all found to be helpful, though their use is somewhat variable. Dr. Foster, would you mind talking a little bit about how you incorporate these therapies into your burn inhalation treatment protocols?

Yes, thank you. It's a good question. We don't have a lot of standards of care for this. We do have a protocol for severe inhalation injury where we use aerosolized heparin. Thank you. And I'm not sure that works really well, but we have some anecdotal evidence that it's semi helpful in some patients. It's idiosyncratic.

It really varies from patient to patient. And then things like bronchodilators and mucolytics, we tend to use those on an individual

basis based on what patients needs are. So if we have thick secretions, then we use a mucolytic. If we think that reactive airways are a problem, then we use bronchodilators.

So it's really largely individualized in my center when it comes to inhaled agents as an adjunct to the treatment of inhalation injury. Got it. Dr. Palmieri or Dr. Rihani, any thoughts on this question, any differences in how you approach these therapies at your own centers? I think this is an opportunity to use your bronchoscopy to help you.

So if we identify a cast situation, an eschar on bronchoscopy, then we'll institute mucumus because there's a reason to do so. The thing to remember is that heparin only works if there's antithrombin 3 there, so you need to make sure your patient has that antithrombin If, however, you don't see a lot in the airway.

And what the patient is having is a reactive airway issue.

So they're acting like they have asthma. That's the time where bronchodilators can be helpful. And that often is not that right off the get go. That often happens about three or four days into it when your patients will suddenly develop bronchospasm and you will actually hear them wheeze.

And it's from the retained particulates, and that's when we will add the bronchodilators. But overall, it's a great way to use your bronchoscopy to help guide therapy. That makes a lot of sense. Thank you. A little bit different than the other two panelists here. We do have a question. quite formalized protocol where we place every single inhalation injury patient on some sort of an inhaled therapy.

So even grade ones get inhaled albuterol or bronchodilators of some And I think the thought process there is that These particulates that we're seeing on our bronchoscopy are irritants and there's frequently a higher risk of that

bronchospasm or reactive airway. Yeah, it usually doesn't show up till day two or three, but oftentimes we've started them day zero on their inhaled albuterol with a protocol set in place for when to deescalate and how to deescalate these things.

Regarding mucolytics, we only use those as needed based off of what we're seeing on bronchoscopy, just like Dr. Palmieri and Dr. Foster were discussing. And regarding our aerosolized heparin, we actually use that for every grade 2 or higher patient. And the reason for such is we were actually having a lot of instances of patients who were forming blood gas in their lungs.

And we figured that, with the risk benefit analysis weighing heavily in the benefit section, why not start these patients early, make sure that this doesn't happen to us again. We had patients that we essentially were in a couldn't ventilate situation, and calling the ECMO team STAT to come to our bedside to save these patients lives.

Once

we initiated our aerosolized heparin, we started to see a lot fewer instances of that. And, you know, something that we do incorporate at our unit is inhaled hypertonic saline. And the reason for that was we were seeing a lot of instances with patients where they were having bronchial edema as a result of the inflammation from the particles.

The inhaled hypertonic saline works to keep the actual bronchial lining from swelling too much. Obviously you're using oncotic pressure there to pull fluid out of the bronchus and into the actual airway, but this requires that You are doing your daily bronchoscopies, you have respiratory therapists who are suctioning frequently, just to keep them from drowning in their own fluid, of course.

Well, thank you. Yeah, that's something I wasn't familiar with myself. Dr. Uriani, who uses conventional ventilation? Yeah, great question. Conventional ventilation and non conventional ventilation. You know, when you look at the data

regarding these things, especially in just any ARDS patient, there is no difference in outcome.

Now, does this mean that we should never use non conventional ventilation? Perhaps not, but more so we should be selecting the appropriate patients for this. Now, APRV is something that a lot of people discuss where we place these patients essentially on reverse IDE ratios. And you have non conventional ventilation.

The goal for this may not necessarily be an improvement in mortality, but more so improvement in clearance, even in some cases, improvement in patient synchrony with the ventilator. A lot of studies have come out showing that this mode of ventilation is a little bit more comfortable for the patient. It requires them to breathe on their own very frequently in order to ventilate appropriately, but there are a lot of options for non conventional ventilation and deciding when to incorporate them is a

patient by patient kind of thing.

Dr. Palmieri. I agree. It's a patient by patient decision. In general, in an inhalation injury patient is not the person to try nonconventional ventilation in if you are not comfortable doing it. If you do nonconventional ventilation or APRV, if you never do it, You shouldn't be trying it on someone with inhalation injury because you won't do it well.

A mode of ventilation that we haven't talked about is the volumetric diffusive respirator, which is an older technology, but it's a combination of a jet and a pressure ventilator, which there is some data that support it can help in severe inhalation injury with, in terms of secretion clearance. It's a very specialized ventilator, and again, if you don't use it, you probably shouldn't.

It is a toolbox item that, in a specialized burn center, it can be very helpful in the management of inhalation injury, particularly in children. At the Arizona Burn Center, we will place the patients on APRV at 100 percent FIO2 for at

least the first eight hours, and I wanted to ask Dr. Foster how he had developed this protocol and what were his experiences so far with this.

Tommy, it's an interesting story how we ended up where we are about 20 years ago, we were using the VDR for a volumetric diffusive respirator, which is a unique and very interesting ventilator. And at the time we were being moderately successful with it, but there were some disadvantages, which I won't go into now.

We had purchased a number of new ventilators, the Servo I ventilators that had APRV or BiVent capability. So we started trying that and within about a month we had transitioned every single one of our VDR patients over to BiVent and we've never looked back. We were able to demonstrate improvements in most every category.

You know, peak airway pressures, mean airway pressures, PF ratios, ventilator associated

pneumonia, barotrauma. Everything like that, but we're really looking at historical controls. Now, APRV has got some really good advantages. It is an excellent oxygenation ventilator. It is pretty simple to use operationally on a day to day basis because you don't make very many changes.

However, there are some real disadvantages. You have to think a little bit differently, particularly when it comes to ventilation and the moves that one would normally make for conventional ventilation are not always appropriate for APRV, and balancing ventilation and oxygenation can be a little bit difficult.

You really can't break the circuit on a consistent basis on APRV. So doing interventions like bronchoscopy may actually be detrimental. People do tolerate APRV fairly well, but some people don't. And sometimes it requires an increased level of sedation and analgesia to get them to be comfortable. But I think the really

important thing is to recognize that it's one way, it's our way.

It works for us the vast majority of the time. But there are times when it doesn't work, and we do go back to more conventional modes of ventilation. We've occasionally gone back to the VVR4, oscillator ventilators, things like that. So, I think that this idea that you have to treat individuals individually, I think, is really important.

However, our outcomes tend to be pretty good. We very rarely have anybody pass away from a pure inhalation injury. And we have only had to refer people to RACMO four times in 20 years, and that's well over a thousand inhalation injury patients. So, bottom line is, it is a good protocol for us, but it's not the only way to do things, and we do modify what we do based on what patients need.

So, let's move on to now a related topic. When do you place a tracheostomy? Dr. Palmeri, what are your thoughts on this? I think you have to do it on an individual

basis, but in general, and this is how I approach medicine as well, if you see that someone's going to be on that pathway towards being on the ventilator for a long time, there's no point in wasting time.

Just get it done. Because the longer you wait, the more potential you have to have some other complication. And so there's some patients with very severe inhalation injury, and they have issues from the get go. Thank you. That waiting doesn't get you anywhere. So those are pretty straightforward. Or someone with a massive face burn that's incredibly deep, that you know is going to require an airway for a long time.

And you do it at the first opportunity when it's safe. And what is safe depends on the patient and the surgeon as well. Again, if you don't do a lot of tracheostomies in edematous patients, you probably should wait a little bit until that edema goes down. If a patient's tenuous on a ventilator, your operative ventilator will not be any better.

In fact, usually

they can't get the same airway pressures that you can, so it may not be safe to do a tracheostomy. Any other thoughts from the other panelists? I do actually have a question for Dr. Palmieri. My question is, when do you decide percutaneous at the bedside versus going to the OR? I'm more of a fan of an open trach.

However, the contraindication to a percutaneous trach is if you cannot intubate them from above. So if your patient is so edematous that could not be re intubated orally, if you had difficulty inserting your tracheostomy, You should not be doing it percutaneously because you would never be able to get the airway if they could not reintubate.

So that's the main contraindication. Thank you. I am in agreement with a lot of Dr. Palmieri's thoughts there. Earlier is better when you're expecting them to be on the vent for an extended period of time. I do want to add that, you know, these trachs, not only are they more comfortable, but in our experience have led to fewer ventilator days for these

patients.

You know, once you're on the trach, you can try taking them off the vent very easily and with very little repercussion because, worst case scenario, you hook them back up and you're doing great. That's a great point, Dr. Riani. It really does shift that risk benefit balance. Sometimes managing burn inhalation injuries doesn't go so well with the peep bladder, cronying, paralysis, steroids.

Sometimes you need rescue therapies. Dr. Riani, what's your position on this? Yeah, good question. For veno venous ECMO, there are indications to start that right and we should all be familiar with these indications. You have a reversible cause of acute respiratory failure. You have some sort of life threatening hypoxemia.

There is some studies that have shown that severe hypercapnic respiratory failure is an indication to go on ECMO. And you've attempted all your safe ventilatory strategies, you've attempted proning, you've attempted placing them on some sort of paralytic, and you are no longer able to stay safe.

So, these are the patients you're starting to think about, should we be initiating ECMO?

For the most part, an inhalation injury, These things don't show up immediately. Inhalation injury is a progressive disease that worsens over the first 48 to 72 hours. So if you're thinking about ECMO by day 3, day 4, then you really should be contacting your ECMO team because once you hit day 7, you're looking at a patient who is no longer going to see some survival benefit from starting ECMO.

So we often contact them early when we think that things are headed in the wrong direction. And in really severe inhalation injuries, things will head in the wrong direction for the first couple of days. almost every time. So once we've contacted our ECMO team, our approach for initiating VV ECMO is actually an early approach for a few reasons.

One, VV ECMO works by placing the patient in series.

With the extra corporeal membrane. So when we oxygenate their blood through the VV ECMO, we're in fact not oxygenating all of their blood. We cannot take their entire circulation and run it through the ECMO machine. There will be some venous mixture.

And this mixture means that we are relying on the patient's underlying, oxygenate their own blood with their lungs. So if you've waited to the point where the lungs are no longer able to oxygenate the blood at all, you're looking at a patient on ECMO who is hypoxemic despite being on maximum BV ECMO.

You have flows of 5 liters and you're still unable to get the patient's saturation above 80. A lot of the studies that have come out about ECMO, they were historically based off of really severe pandemics. So for example, we have the influenza pandemic back in 2008 or 2009 when the paper came out regarding ECMO showing some survival benefit.

And those are the

patients that when they studied them, they placed them on ECMO early. And those are the patients that did better for the most part. In our experience for the patients we placed early on ECMO, and this is day three or four. You're looking at pretty good survival outcomes and pretty good overall outcomes for the patient.

The longest I think we've had somebody on ECMO is about 73 days. And that patient actually ended up coming off of ECMO and getting extubated, doing relatively well. Obviously they have some underlying pulmonary fibrosis as a result, they become lung transplant candidates, but it is better than the alternative.

Well, for some people, maybe better than the alternative of death, right? These are all individualized decisions that have to be run through the ECMO team. And if the ECMO team is in agreement, and you feel like this is a reversible cause of respiratory failure, which it usually is for patients with inhalation injury, then you're looking at good outcomes.

When I was

a third year medical student, the first patient that I saw on my trauma rotation was a patient that was in the burn ICU in the tub room. He had been unfortunately involved in a roller or a jeep accident, you know, severe high TBSA full thickness burns. Certainly concern or found inhalation injury he was getting escharotomies over his chest.

What are your thoughts on how to manage these patients with burn injuries plus slant, or I guess sometimes penetrating injuries? Do you have specific protocols in place at your institutions, Dr. Foster? Terrific question. And these patients are really challenging. Again, I think we come back to, you really have to manage them individually.

We're a busy level one trauma center, and so we have a fair number of burn trauma patients, and in general, trauma trumps burn for most injuries. It gets really complicated if you have a large percent total body surface area burn superimposed on a multiply injured trauma patient and deciding what comes first and

prioritizing and the how do you fit in fluid resuscitation and burn excision.

And then, if you start talking about lung injuries and pulmonary contusions and chest tubes, in addition to smoke inhalation, it gets very complicated in short order, but we have a fair amount of experience managing these patients. And again, all I can say is, you just have to really individualize them.

Any other thoughts to the panel? We actually looked at the combined trauma and burn databases, and at about 40 percent burn, the burn becomes a more significant determinant of long term survival. However, it does depend on your traumatic injury. The biggest issue for us is when you have a traumatic brain injury combined with a burn injury.

The LD50 for that is a 25 percent burn overall. So half the people with a traumatic brain injury and a burn of 25 percent in size will die from their injuries. And I think part of that is because in burns we need to give a bit more fluid, right? In

traumatic brain injury, you need to give just the right amount of fluid.

And when you get that combined injury, that is more of an issue. So this is where we actually work very closely with our traumatologists and do some additional monitoring with intracranial pressure monitors because You can literally herniate from your burn resuscitation if you do it the way we normally do it.

So that is one example of an individualized approach to burn and traumatic injury. We'll move on to our last topic, future of burn antelation injury management and research. What are some recent advancements or innovations that have been made? We'll start with you, Dr. Ubiani. You know, a lot of the advancements and innovations in burn inhalation injuries are looking at how to successfully prognosticate these patients and then, of course, how to successfully

prevent the inflammation that results from being exposed to such harmful caustic substances.

For the most part, a lot of the biomarkers that we see that these patients are being tested for. are biomarkers that can be targeted by some sort of medical therapy. We're hopeful that we can start these patients prophylactically on inhaled or IV therapies that can prevent the resulting inhalation inflammation that we see.

And if we can prevent the inflammation, a lot of the respiratory failure, acute respiratory distress syndrome that we see in our patients with severe inhalation injury can be prevented. I'm excited to see what these results are, and I'm excited to test out some of these things in our patients, especially those that have an extremely high risk of mortality.

And you're talking about patients with greater than 30 percent TBSA burn, with concomitant grade 3, grade 4 inhalation injury.

I think you raise a really important question. We are overall lacking a biomarker that tells us the severity of inhalation injury. There's a whole bunch of them that are in process in the lab and they work great in mice and rats.

But they have not made the transition to human beings yet. They show promise, but they have not actually made it to prime time. In terms of imaging techniques, one would think that a CT scan would be extremely helpful. But we have yet to have evidence that CT scanning accurately prognosticates for someone with an inhalation injury.

So I think one of the big challenges we have is to find something that can accurately prognosticate. The biggest bonus we've had is just the ARDSNET protocol for low pressure ventilation, avoiding iatrogenic injury. I think that was probably the biggest step forward that we've made in inhalation injury.

And it had nothing specific to do with inhalation injury. But it had everything to do with how we were supporting people through their

inhalation injury. We've actually seen a few studies that have come out that have shown PF ratio is equally as good, if not better than the grading on bronchoscopy at prognosticating these patients.

Yeah. When you think about grading, it sounds very robust, right? You grade one, two, and three. But if you actually look at the criteria, it's what you think you see. There's not very sharply defined measures. It's not like a number. It's still an impression. That's variability is an issue. Exactly. Even grade 4 says complete endoluminal obstruction or obliteration.

I mean, we've seen people that come in with endoluminal obliteration because of all the soot, but once you clear them out and you look under all of that, It's not as bad as you thought initially. And this abbreviated injury score, if you look at the small texts and the small print, you'll see that you're not supposed to change the grade of injury after your first bronchoscopy, this bronchoscopy that was

initially done.

And the grade you gave is the grade they will stick with for the rest of their stay. So a grade four inhalation injury with complete endoluminal obstruction may not be as bad as somebody who's. severely erythematous throughout their lung and has a grade two or grade three for someone. I think this would be a great area to develop, you know, kind of a combined score where you take bronchoscopic evaluation plus, you know, maybe some of the other EF ratio, maybe other biomarkers that are in development.

You know, one example of active area research is people setting the effect of smoke inhalation injury on the lung microbiome. We think of the gut as having a microbiome, obviously, but so does the airway. And that can be disturbed in the setting of inhalation injury. I think the lung microbiome being injured for smoke inhalation could be very well all the same pathophysiology as the gut microbiome.

Let's put it this way. If at that age were to come to you and and say, okay, here is funding for research on inhalation injury, what topic would you focus on?

You're looking at years, if not decades, of looking for something that could indicate. An area of study and then following up on that and we're so far behind in inhalation injury, especially when you compare it to other things like acute respiratory distress syndrome, which honestly, I think, is where most of the research should be going because the underlying mechanisms are very similar.

When you're looking at these patients, the same thing is going on with our patients with ARDS secondary to pneumonia, right? There's some caustic substance in their lung that is causing this terrible inflammatory response. And I would probably focus in the same places that these patients with ARDS are being focused.

Well, I'll give you my two cents. Take it what it's worth. We have a definition problem to define inhalation. We've actually defined four different injuries as inhalation injury, and that's going to make it very difficult to globally

identify mechanisms to solve inhalation injury, because what works for one of those injuries is likely not to work for another.

We have to come together and decide how we can consistently identify inhalation injuries so that our studies can move forward and be meaningful. Until we do that, we're going to be very squishy in what we can accomplish. There's a lot of great work being done right now on inflammatory biomarkers for the chemical type of inhalation injury, so when the smoke gets down into the lung parenchyma.

So there's some very elegant inflammatory markers that are being investigated. That needs to proceed. There's actually some really cool work in exhaled breath analysis, so you can tell what that patient has inhaled, and that may be informative as to what kind of treatments you may need. And there's also some biomarkers in the exhaled breath analysis.

That's kind of a cool thing. We have to prove heparin, yes or no, because really the aerosolized heparin was

only shown in one small, randomized trial in children. And subsequent to that, there was a negative aerosolized heparin trial. The final one you guys already asked us about, and that's long term outcomes.

Their patients lives aren't done when they leave our units, they're just starting. And what's happening to those patients, and is there something we can do in the hospital to make their long term outcomes better? I want to again thank Drs. Foster, Palmieri, Bianni, Liam, and Holly for taking the time out of their busy schedule to make this wonderful podcast for general surgery residents, medical students, and future burn surgeons alike.

This is Tommy Tran signing out. Until next time, remember to dominate the day.