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Julie Bastarche, MD: [00:00:00] Sepsis, as you know, is a systemic problem, and that means it occurs all over the body, and in some patients, you know, 30 to 40% of patients, that body reaction damages the lungs, and we call that acute respiratory distress syndrome or ARDS. 

Nicole Kupchik: This is the sepsis spectrum, a podcast about antimicrobial resistance, sepsis, and how to expect the unexpected in your practice.

[sponsor acknowledgement]: Sepsis Alliance gratefully acknowledges the monetary support provided by Vantive for this podcast series. 

Kristan Seaford: Hi, I’m Kristen Seaford, and I am a sepsis survivor. Nine years ago on November 24th. 2013, I was about to have 32 people for Thanksgiving dinner that week. My kids, I have five kids, they had been sick coming in and out of the house all week with strep throat, [00:01:00] flu, colds, you name it.

So I should have known that I would likely get sick, but I just kept going. Moms don’t get sick days. And so. I did what I always did and I kept going. But Saturday night I started to feel pretty sick, started feeling achy, um, a little feverish and had a, a bad sore throat. So when I rolled over on Sunday morning and texted my friend, sorry, I can’t run today.

My husband knew that something was really wrong, so I asked my husband if he would go ahead and take all the kids to church for me so that I could stay home and rest. They weren’t gone two hours if that, and they came home and they found me. [00:02:00] Unconscious and unresponsive. I was coughing and gasping for air.

My husband called 9 1 1. He started what he knew of the CPR, which wasn’t much, and zoomed me off to the hospital. We got there long enough for them to test me for the flu, which I was positive. They also tested me for strep throat. I was also positive, and when the chest x-ray came back, it showed that I had a pretty severe case of double pneumonia, and then the blood work came back and showed that indeed the infection, the strep infection had gotten into my bloodstream, which we all know now anyway.

Is a sign of sepsis. They whisked me away to the hospital in uptown Charlotte. I was on full life support. They put me [00:03:00] into a rot prone bed, which is where your head is lower than your feet, and they let the pneumonia drain out of them. Such that the antibiotics could work better. They also gave me some medications that were experimental.

Slowly but surely, I came around. I started to breathe on my own. Once I woke up, it was a great celebration. That was actually Christmas day of 2013. It was our Christmas miracle, right? But it didn’t come without its costs. And the medications that they gave me, actually, they are known to work by taking the blood and treats oxygen away from your limbs to save your organs.

And that is exactly what happened. I lived, but in effect, my hands and feet died. They were black and gangrene, [00:04:00] twisted. So a month after I woke up. They did a big, quadruple amputation surgery. I lost both arms below the elbow. I lost my left leg below the knee, and they were able to save part of my right foot.

I have wonderful prosthetics that can open and close.

Dinner on the table most nights and make sure my kids pack their lunches, take care of myself and back to work full time. My career before all of this happened was to be a mental health counselor, and so I don’t have hands and feet, but I still have ears, and I am a good counselor, a better counselor.

Because of all that I have gone through, I struggle a lot. [00:05:00] I also succeed a lot, so I count myself lucky to be able to help.

Nicole Kupchik: Hi everyone, and welcome to the sepsis spectrum. I’m Nicole Kupchik, critical care nurse, clinical nurse specialist, and your guide through the unpredictable. World of sepsis, or as we like to call the season sepsis and multi-organ dysfunction syndrome. As we close out season two, I’ve been thinking a lot about the fragile rhythm.

We’re all so lucky to have that quiet, automatic movement between inhale and exhale that carries us through every moment. Breathing is arguably the simplest thing we do, and the easiest thing to forget until it’s gone. The clip you just heard was from Kristen Seaford, a mother of five, whose life forever changed.

When flu and strep turned into sepsis. She went from preparing Thanksgiving dinner to [00:06:00] fighting for every breath. Kristen’s story is a. Scary, but incredibly important reminder to us all that conversations like the ones we’re so fortunate to have on the sepsis spectrum are so important. ’cause honestly, you never know when context will be key.

And looking at sepsis, the longs are often the stage where it takes place with clear visibility. It’s where infection meets inflammation, it’s where oxygen turns into chaos. And for many, it’s where survival begins. When sepsis overwhelms the lungs, we see the full force of multiorgan dysfunction, oxygen drops.

Carbon dioxide rises, the alveoli collapse and the cascade that follows can leave even the strongest patients relying on machines to breathe to help us close season two with a clear view of the lungs during such a critical stage. I’m joined by Dr. Julie [00:07:00] Bastarache, professor of Medicine, allergy pulmonary and critical care at Vanderbilt University Medical Center.

Dr. Bastarache’s research reveals how inflammation and capillary leak destroy the delicate barrier between air and blood, and how those same processes shape recovery long after the ICU. Take a breath, stick around and join me in learning this connection between sepsis and ards. We’re gonna chat about. Some strategies to treat patients who have decompensation.

And then we’re gonna talk a little bit about mechanical ventilation. So we’re gonna dig a little deeper into the clinical aspect of sepsis and lung injury. And then in addition, we are gonna hear some of the amazing research that Dr. Bastarache is involved with. So stick around. We’ll be right back with Dr.

Julie Bastarache.

Hi everyone, and welcome [00:08:00] to the show. I am so excited to be joined today by Dr. Julie Bastarache, who is a critical care physician, and a physician researcher who is gonna share a lot of knowledge and what she’s working on at 

Julie Bastarche, MD: Vanderbilt University. So welcome to the show. Thank you. I’m really excited to be here and talk about the lungs and sepsis.

So thank you for having me. 

Nicole Kupchik: Yeah, I, you know, you’ve been doing some amazing work. Um, can, do you mind telling the audience what your role entails? Because you a very unique role where you spend about 75% of your time doing research, about 25% at the bedside. So can you kind of walk us through like what, let’s just say like six months working looks like for you from both research and clinical perspective.

Julie Bastarche, MD: Sure. So, um, I’m a physician scientist, is the type of job that I have. Um, and it’s exactly what it sounds like. I’m a physician, so I went to medical school. I’m a doctor and I take care of patients. I’m a, uh, an intensivist critical care [00:09:00] physician. I, uh, my clinical practice is at the VA hos. Hospital in, in, uh, here in Nashville, Tennessee.

And I spend six weeks a year on clinical service in two week blocks. And then the scientist part is being a scientist. So I spend the rest of my time doing research in a large research lab. And my lab is located at Vanderbilt University in Nashville, Tennessee. And those two, um, uh, facilities are right next to each other.

So, um, it’s really kind of two jobs. Uh. Put together, but they really integrate very nicely. So it’s a very natural, um, it’s a natural pairing. Um, so they’re physician scientists at all academic large medical centers doing research and taking care of patients. 

Nicole Kupchik: Okay, so I’m dying to know what are you working on from a research perspective?

Julie Bastarche, MD: So I’ll first tell you a little bit about how I approach research questions, and this comes from being a physician scientist and so I am, um, a lot of people have heard the term translational science in that translation means bringing, uh, information [00:10:00] in from one sphere into another. And when people think about translation, they think about translating from the bench.

So basic science discoveries and mice and cells in bringing that. To the clinic. I kind of flip that, um, on its head and do what I call reverse translational science. So I get inspired by patients that I see in the hospital, um, with various critical illnesses, primarily sepsis and organ dysfunction. And I take observations made in patients and I try, I take those back to my lab.

Study it in Mice and cells, um, and try to figure out the why of what’s happening. So why do some patients who, um. Get pneumonia developed sepsis. Uh, why do some patients who develop sepsis get bad lung injury, but not bad kidney injury and so forth. So that’s what the, that’s the reverse translational piece.

So making observations at the bedside and bringing them back to the lab to really try to understand them with the goal of [00:11:00] generating fundamental knowledge that can then help us go back to the patients with new therapies or ways to prevent these problems. So I guess what I would love to know then now is what are you working on?

Sure. So, um, working on a few things. Um, so one of, uh, my more recent projects is looking at these new diabetes medicines like Ozempic, the GLP one receptor agonists that, um, are, have really transformed, uh, treatment of diabetes and obesity. It turns out that those medicines have, um, some really unique effects on.

The immune system cells that line the blood vessels cells in the lung and they actually can protect these cells and organs from injury. So I’m actually studying these, uh, GLP one receptor agonists, specifically liraglutide in sepsis and in our mouse models of sepsis. It actually protects mice from getting organ injury.

Um, and we’re really trying to work out the mechanism of how that works. [00:12:00] Another large area of interest in my lab is understanding how, um, hemoglobin that is. Escapes from red blood cells. So hemoglobin is in red blood cells. It’s the iron containing protein that carries oxygen, uh, to organs and carbon dioxide away from organs.

And that exchange happens in the lung during sepsis. It’s a unique situation where the red blood cells bega become very fragile and they. Burst open, releasing cell-free hemoglobin into the circulation, and some of it gets into the lungs as well, and that hemoglobin, when it’s outside of the red blood cell is very, very toxic.

So we’re trying to understand the, the mechanisms of, of hemoglobin toxicity and the endothelium and epithelium. That’s fascinating. Yeah. These, these two big projects were inspired by things see, that we saw at the bedside. So, um, you know, we were studying blood samples and lung samples from patients with sepsis and a RDS and found that they actually had very [00:13:00] high levels of.

Cell-free hemoglobin in them. And so we were wondering what the hemoglobin was doing there. And it turns out that the hemoglobin is injuring cells and organs. And likewise, we had looked in some clinical data sets of people that are on, uh, GLP one receptor agonists like ozempic. And it turns out that if you look in large clinical data sets, um, of patients who have sepsis, they get less organ injury.

So now we’re taking that back into the lab and really studying why that happens. 

Nicole Kupchik: I mean, it’s fascinating. I, you know, a lot of us who work in a medicine in healthcare get updates from like Medscape and different sources like that, and I, I swear every week there’s some big breakthrough with these GLP one drugs that is just mind blowing.

You know? I mean, truly it seems to be affecting, I it’s got massive anti-inflammatory effects, sounds like. Yes, 

Julie Bastarche, MD: yes. And it’s, 

Nicole Kupchik: they’re very protective to the body as a whole. 

Julie Bastarche, MD: Exactly, exactly. So you’re just gonna start 

Nicole Kupchik: spraying in the air, I don’t know. 

Julie Bastarche, MD: Well, and what we [00:14:00] ultimately would like to do is really understand how and why it’s working.

Um, the, these GLP one medicines like liraglutide are working in different cells and organs so that we can then, um, figure out exactly which patients with sepsis we may wanna target with very short treatments of these medications. 

Nicole Kupchik: Well, and that’s the thing you really wonder about, like could a drug like that help in the acute phase or are the benefits seen over time?

You know what I mean? Is it just like the patients who are on these drugs? Who then get sick have benefit, or is there acute benefit? Do you have, do you have any idea about that? 

Julie Bastarche, MD: So, um, we have, um, we’ve got some idea from patients in terms of people who are on these medications. Um, we have, we’re, we’re very fortunate at, at Vanderbilt.

We have a huge, um, uh, data resource here of. 3.8 million, uh, patient records at Vanderbilt that we can study for research purposes. And it’s completely [00:15:00] d de-identified. We don’t know who the patients are individually, but we can look at them as a group. And we did a study where we looked at all patients that are on these GLP one receptor agonists.

And we compared them to other groups of medicines that are given to the same types of people. So things that are called SGLT two inhibitors and DPP four inhibitors. So when you look at all of these patients, we, we, we find patients who are on these medicines and then, um. Of all the patients that are on these medicines, how many people get sepsis?

And it turns out that people who are on the GLP one medicines are less likely to come into the hospital with sepsis. And then, um, if patients do get sepsis, they’re less likely to, um, get organ injury. So their kidneys in particular seem to be protected. Now there are a lot of caveats. These data, right, they’re retrospective, observational.

So it does seem like if people come into the. On these medicines in these large, you know, uncontrolled studies that we’re looking at, [00:16:00] they are protected and, um, but we can really test. This is why I think, um, mouse models in particular are very, very helpful and really important because we can test this specifically in our mouse models.

So in studies that we’ve published, we tested the sort of pretreatment, preventive, um, role of these medications. So when we give our mice. These medicines for three days before they, uh, we make them septic, they survive better and have less organ injury. And then in a, and we’ve published those results in companion studies that are not yet published.

We’re addressing the other question of, okay, if someone comes into the hospital. Not on these medications and we give them medications in the acute setting, can we have a positive impact? And we also see that in a treatment modality like that, um, in our mouse models, these medications are protective. So we think it’s probably a combination of both.

Um, and we’re really excited to continue these studies, [00:17:00] um, in mice and. Cells to figure out exactly what, where, when, why. Um, and then we can be very specific about who, what patients we might target, um, with these medications in the future. 

Nicole Kupchik: I, I think this, this is really exciting because I think in sepsis, I feel like over the years, because I’ve been doing this three decades, right?

I just, like, over the years we try to look, we constantly on the search for the silver bullet, right? And, you know, I have this, I, when I talk, I have do presentations. I’ve got this slide, I call it the sepsis, grape research graveyard of things that we’ve tried and just, you know, like standalone. If they don’t work.

But you do wonder some of these things in combo or like a, a GLP one that has an overall anti-inflammatory effect. Like is there some promise there, which is super exciting. 

Julie Bastarche, MD: Absolutely. And I think the other piece of that, and you know, we, you know, people in the sepsis and in organ dysfunction field are intimately familiar with the graveyard of failed therapies.

And I think there, there are two [00:18:00] reasons for that. Number one, um, we don’t. Really know the mechanisms of how these things are working specifically in, in regards to sepsis, but also, um, uh, in the sepsis field where the sepsis research field is moving in Really exciting new directions is really trying to understand, um, the specific characteristics of each and every patient with sepsis.

Sepsis is a very broad, um. Umbrella term that is really, it’s, it’s a clinical syndrome. So, and what that means is patients who have a variety of different, um, signs and symptoms come in and we, and if that, those are due to an infection, we lump that all as. Sepsis. But in some patients, sepsis might be a really, really overactive immune reaction.

In other patients, it might be an immune reaction that’s not strong enough. And then yet, in other patients it might be that the lining of the blood vessels or the endothelium gets really damaged and that leads to [00:19:00] leakage of fluid into organs and organ failure. So we use the term sepsis to cover a lot of ground, but within sepsis there are likely different.

Pockets, um, or different phenotypes of patients. And until we really can understand, um, these different, um, kind of buckets of sepsis, we’re not good. ’cause they’re, you know, a, a medicine that reduces inflammation is only gonna be helpful. If you are giving it to a patient whose sepsis is driven by overactive inflammation.

So that’s another really exciting area. Um, and there’s a large consortium study going on across the country supported by the NIH to try to answer that exact question. When we say sepsis, it’s not just one thing, it’s many things and we’re trying to figure out what those many things are. So it’s a combination of finding the right patient in the right treatment, um, at the right time.

But we’re gonna get, I think we’re gonna get there within my li within my lifetime. I think we are gonna have treatments for sepsis. 

Nicole Kupchik: I hope so. I, I think it’s exciting. And you know, we need people [00:20:00] like you who push things and ask the questions and study the que. I mean, you are so, your work is so important in the world of sepsis and medicine.

Then, so, all right. Well, I wanted, um, kind of shift gears a bit and let’s talk about the lungs, because you’ve done a lot of work with the lungs and specifically the connection between sepsis and lung injury. So can you just briefly explain, um, to the audience just what’s happening in, um, patients who are septic, who then develop lung injury and then arts?

Julie Bastarche, MD: Sure. So, um, sepsis, as you know, is a systemic problem, and that means it occurs all over the body and in certain, in some patients, you know, 30 to 40% of patients that react, that body reaction damages the lungs. And we call, call that acute respiratory distress syndrome or a RDS. Um, in A-R-D-S-I like to think about it at sort of like three different.

Levels. So there are clinical features that [00:21:00] characterize A RDS and I’ll talk about those. There are physiologic features and then biologic features. So, um, first the question of physiologic features. So what is a RDS? How do we find, how do we diagnose A RDS? Well, the clinical features are pretty simple, so, uh, because it’s a problem of the lungs, we see people who have.

Respiratory distress or respiratory failure, they’re breathing really quickly. They say they can’t breathe. They’re very short of breath, and that’s accompanied by low oxygen level. So when you go to the doctor, the doctor puts that little thing on your finger that’s measuring the amount of oxygen in your blood.

So if you have respiratory distress plus low oxygen. In the setting of sepsis, um, that is someone who likely has a RDS And to diagnose it for sure, we get a chest x-ray and we’ll see that the chest x-ray, the lungs are filling up with fluid. So the clinical features are low oxygen, rapid breathing, and respiratory distress.

In someone who has a, an underlying risk factor. And then I [00:22:00] think about physiologic, um, changes. So physiology is sort of the mechanics of how the body works. So the heart pumping, the blood, flowing, the lungs, breathing in and out. Um, and what we see in, um, A RDS. Is a couple of things. First, because the lungs are filling up with fluid, it’s kind.

You can kind of think of it like a sponge is real squishy and, and it’s real soft and bounces back, but when it’s full of fluid you have to squeeze it really hard to squeeze that fluid out. When the lungs, which are really soft, a nice soft sponge, when they fill up with fluid, they get very, very. Stiff and when the lungs get stiff, it’s really hard to blow air in and out.

So it takes a lot of work and a lot of pressure from, um, the breathing machine or mechanical ventilator to blow air in and out so the lungs get stiff. We call that decreased compliance. Also what happens, because sepsis is a, a problem with a whole body. One of the things that gets activated during sepsis is the coagulation or blood clotting system.

So [00:23:00] the coagulation system gets activated throughout the body. Little blood clots form everywhere, including in the lungs. And that means, uh, we have something called, uh, dead space. And dead space is, are areas of the lung that are breathing air in and out, but blood’s not flowing. To exchange, um, gas, and that’s one of the reasons that people breathe so quickly, um, is because a lot of the lung is essentially non-functional.

So we have decreased compliance and increased dead space as the physiologic changes. And then there are a host of biological changes. We see breakdown of the cell barrier between the blood and the air. Base and that lets plasma and other fluid leak into the lung. We see inflammatory cells coming into the lung and damaging the lung.

Um, and those small blood clots like I mentioned before. So that’s kind of how I think about, um, lung injury or on those three levels. 

Nicole Kupchik: Okay. Well, and I think that’s a, a great explanation for both the clinician and non-clinician because it’s not [00:24:00] uncommon to see lung injury in patients who do end up getting really sick with sepsis.

Well, and I think that’s really interesting because we know pneumonia is a very common reason that patients. End up getting really sick with sepsis, with num, one of the top sources. So, um, you know, so we definitely see lung injury. All right. Well, what we’re gonna do is we’re gonna take a break and when we come back we’re gonna dive into the clinical treatments that are used for lung injury.

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And now back to the show.[00:25:00] 

All right, welcome back. Now we are gonna dive into just identification and therapies for patients who are experiencing lung injury in the setting of sepsis. All right, so let’s say we’ve got a patient who’s getting progressively short of breath. We’ve already talked about some of the diagnostics we’re gonna get.

Uh, what are your thoughts early on? High flow nasal cannula? Yes. Beneficial yes or no? 

Julie Bastarche, MD: Sure. So high flow nasal cannula is, um, and is beneficial in terms of being able to support patients and perhaps stave off intubation. So it’s sort of in the intermediate between regular nasal cannula, just the small prongs, high flow nasal cannula, um, and then more invasive, um, methods of ventilation.

Uh, this high flow was used very, very broadly in patients with COVID induced a RDS. And sepsis. And that’s where most clinicians, including myself, [00:26:00] really got a lot of experience with it. Um, and that was a little bit of a unique situation. And so the way I think about these different, um, levels of oxygen supplementation are, they really are just.

It’s like crutches when you break your leg. It’s helping to support the patient at whatever level they need while the underly, while the, the, um, healthcare team is treating the underlying problem that’s driving the A RDS. So high flow is a great bridge between regular nasal cannula oxygen and more invasive, um, invasive measures.

But high flow alone, it’s just a supportive therapy. It’s not a treatment. Okay, BiPAP. 

Nicole Kupchik: BAP. So, so technically we’re supposed to say BPAP, right? BiPAP is a brand, but BiPAP, what do you think? Bilingual. Oh, 

Julie Bastarche, MD: I’ve, I’ve never heard of it called BAP. Um, no one ever does. Right, right. That’s so, that’s interesting. Yes.

Um, I call it BiPAP. I didn’t really realize we all, it was a brand name, I guess. I guess that’s like cl. Kleenex, you’re not supposed to say Kleenex because that’s a brand name, [00:27:00] but I call it BiPAP. So BiPAP as you know, um, is the ne kind of the next step up. So if people are on regular oxygen, their oxygen level’s still low.

We try high flow nasal cannula. If their oxygen’s still low or if their work of breathing is really hard. You know, imagine after you’ve just gone out and you’ve had a really hard. Swim or you’ve gone and run really fast, you’re huffing and puffing. That’s what it feels like for patients who have a RDS and lung injury.

Um, and BiPAP can help both with oxygen, but also that work of breathing. It’s sort of like an assist for breathing. So it’s using a face mask to, to deliver a little bit of pressure and really help, um, people breathe more comfortably. And again, it’s just the next level after, um, after, uh, high flow nasal cannula.

And if. The underlying problem and the underlying lung injury that’s going on can, um, uh, turns around in that time period. Some people don’t need to go beyond BiPAP, but it’s just the next, it’s sort of the next step in [00:28:00] oxygen support. 

Nicole Kupchik: All right, so then the next step beyond that, if the patient continues to deteriorate, would be obviously mechanical ventilation.

So. Okay, so, um, I came from an LPV, actually, my hospital was one of the trial sites in the Arts Net trial a long time ago, uh, for lung protective ventilation. Uh, so where we use lower tidal volumes, then you use PEEP to improve oxygenation. Um, what, what’s, what’s your hospital? What do you, are you LPV or a PRV or, uh, some other way to mechanically ventilate?

Julie Bastarche, MD: So I went to medical school in the 19 hundreds. Um, and um, also, I like this with the young ones, say the 19 hundreds. I also, um, uh, at, I was at Vanderbilt for all of my training and Oh, okay. I was part of the team, well, a part of I, the not part of the team, but the attendings at Vanderbilt and the people who were teaching me were the people that were leading the arts net.

Low TAL volume trials. So Art Wheeler and Gordon Bernard were my mentors and [00:29:00] attendings when I was training. So low tal volume ventilation has been part of my practice for, um, for, you know, 25 year, the 25 years I’ve been doing this. And what, what we know for sure is that, um, when you use low tidal volume ventilation, you save lives.

So it’s a very, very simple, um, uh, a very simple way to help. Improve your patient’s chances of surviving. So, um, that is standard, standard practice. And you, I, I learned from Art Wheeler. He, he was an amazing mentor and teacher and colleague. Um, he took a very simplistic approach to mechanical ventilation, which I really like.

You know, there’s all kinds of fancy modes, A PRV, and you know, it may be that for some patients those modes work better, but. Art Wheeler always taught me, um, that you could take just your standard of cyst, control ventilator and make it look like any other mode of ventilation. Um, and there’s [00:30:00] really no benefit, at least mortality benefit for these other modes of ventilation.

But this is a very active area of research. Um, you know, again, coming, getting back to this idea of the right treatment for the right. Patient personalizing the ventilation strategy. But for right now I just use assists control, low tidal volume ventilation for my patients with A RDS. 

Nicole Kupchik: Yeah. Well you know, it’s interesting ’cause I, you know, over the years I’ve done a lot of work with mechanical ventilation and um, a lot of the research shows the best mode is the one you know, how to use.

Julie Bastarche, MD: Absolutely, 

Nicole Kupchik: yeah. You know, there’s just a lot of specifics. For example, A PRV, it’s a spontaneous mode of mechanical ventilation, therefore you cannot use paralytics. You know, and it’s just like little things like that, you know, that are just important, um, idiosyncrasies to understand. 

Julie Bastarche, MD: Right. And I think the, the other thing that’s interesting about, um, that we actually learned from the arts net, the arm study, the low title volume study, um, that we were just talking about is, you know, we clinically we use [00:31:00] oxygenation like how much oxygen we’re able to get into the body as a marker of how, how well our therapies are working.

But the really fascinating thing, if you really, if you read the ANet study, the low total volume study in great detail. Um, you’ll, you’ll notice that the oxygen level of the patients on the high tidal volume was actually better than patients on low tidal volume, but the patients on low tidal volume also survived more.

So, um, so that. That taught us a really important lesson that things that improve oxygenation, um, don’t necessarily lead to improved survival. So I think what a lot of these modes of ventilation do is they actually increase the oxygen level, but they’ve not been shown to translate into benefits in mortality.

Nicole Kupchik: Yeah, I think that’s a really good point. I know, uh, a lot of the intensivists I’ve worked with over the years, we always say more isn’t better, you know, and just shoot for good enough. Support, but more isn’t always [00:32:00] better. That’s right. All right. Okay, so let’s talk about 

Julie Bastarche, MD: peep. Why are we using PEEP in Arts?

Peep or Positive index. Expiratory pressure, um, is a, is there, there are several, several reasons that we use it. Number one, um, when patients get a RDS, they lose surfactant in their lungs. So surfactant is like the soap. Soap essentially that helps to keep your, um, your lung open. Um, and the airspace open that when that surfactant goes away, the airspace collapse and get real sticky.

So peep gives a little bit of pressure to kind of pop those airways open. Um, and that also can help drive out some of the fluid in the lung. So it, it helps with those physiologic, um, changes. Also, um, peep is helpful in a RDS because when we’re thinking about trying to improve oxygen when someone’s on the ventilator, there are only two things that in that can increase the amount of oxygen you’re getting into someone or delivering to someone.

One, you can [00:33:00] turn up the oxygen flow, so the percent oxygen. Uh, but also the other thing is increasing mean airway pressure. So the pressure that’s in the airway over the whole course of a mechanical ventilation breath. So if we add peep. Um, to, um, our ventilation strategy, we’re increasing the mean airway pressure and increasing oxygenation.

Nicole Kupchik: Okay, let’s, and what’s the highest PP you’re seeing clinically? I know like the pandemic was a whole different era, right? But in general, in, um, patients who have sepsis and ard. 

Julie Bastarche, MD: Yeah, we try to, um, you know, there’s, we try to get to the sweet spot. Uh, so, you know, standard IT and the ARD net study, um, the low tidal volume study that we talked about helps to titrate peep.

So as you’re increasing the amount of oxygen you’re giving, you need to increase the amount of. Peep to help that oxygen work better. They kind of go hand in hand. Um, and we just use as much peep as we need to get the oxygen to where it [00:34:00] needs to be. So, you know, someone who has very bad A RDS may be on 1416 of peep, more mild a RDS, maybe five of peep.

But it’s, um, it’s usually, you know, this is something where you have to go to the bedside and really spend time with the patient and adjust the ventilator to try to get to that perfect spot. 

Nicole Kupchik: Yeah. All right. And then, um, just some other vent settings, tidal volume, we usually start at six mils per kilo.

What, what’s the lowest you’ve seen clinically on tidal volume? 

Julie Bastarche, MD: Right. So, um, I, I try to shoot from somewhere between four and six, um, ccs per kilogram with standard assists control ventilation. Now there are, um. There are high frequency oscillatory ventilation and things where the tidal volume is teeny, teeny, teeny, and the lung is like sort of almost hyper inflated with little volumes, but with just a standard cyst control.

Um, mechanical ventilation, anywhere from four to six, um, ccs per kilo. And I usually start at [00:35:00] six and then look at the plateau pressure and if the plateau pressure is under. 30, I’m okay with six. If the plateau pressure is higher than 30, I, I, I dial down the, the tidal volume. And we know from studies that having a little bit of hypercapnea and a little bit of acidosis is actually okay.

And we, as you know, we call that permissive hypercapnea. That’s okay. And that’s actually preferred, preferred to have that, that have very high pressures in the lung that cause further lung damage. 

Nicole Kupchik: Yeah. And, you know, and what, like what c2 if they don’t, if the patient doesn’t have an head injury and ICP issues, what CO2 level are you like, Ooh, this is getting really high, 

Julie Bastarche, MD: I mean.

Below a pH, it’s really the pH that I’m more concerned about. So if the pH, you know, normal pH is 7.4, if the pH is getting into the 7.1 range, then I start to get a little bit concerned. Um. 7.2, 7.3 I don’t [00:36:00] really worry about, but you know, a lot of these changes that we’re seeing in CO2 and oxygen, uh, really they’re, we’re, we’re kind of limited in how we can respond to those because they’re being driven by the underlying disease that’s happening.

So, you know, we do the best we can, um, you know, to, to, to maximize oxygen in maximize CO2 out at the same time that we’re trying to not injure the lung anymore. 

Nicole Kupchik: Let’s talk about just briefly, some other therapies that we’re using at the bedside. I’ll just kind of name ’em and we can kind of, maybe you can give your thoughts.

Um, oh, first of all, proning. 

Julie Bastarche, MD: So Proning, um, is, um, one of the therapies that has shown to improve outcomes in patients in certain situations. I think the problem with Proning, um, is just like we were talking about earlier. You know, the mode of mechanical ventilation that works the best is the one that you know how to use.

Proning works. Best if you’re comfortable proning patients, right? So, [00:37:00] so places that, um, prone patients a lot, um, uh, in general will have better outcomes. They’re more accustomed to the therapy. In my toolkit of taking care of a RDS and severe hypoxemia, I still use proning as a rescue therapy. It’s not part of our standard practice.

Um, where I, where I practice. 

Nicole Kupchik: Okay, great. And I totally agree ’cause it’s not easy to prone a patient who’s on a ventilator on lots of infusions and things like that. All right. Okay. Let’s see. What about, um, inhaled, uh, pulmonary vasodilators? 

Julie Bastarche, MD: Yeah, pro prostacyclin and nitric oxide. Those are, um, those are helpful in patients who have, uh, refractory hypoxemia or low levels of oxygen that, you know, you’ve, you’ve done everything you can with the ventilator.

Um, I, the first thing I go to is paralytics. We’re probably gonna ask me about that in the, in a minute. So, absolutely. I paralyze, I paralyze people for, you know, if I get to a point where I’m on a hundred percent oxygen, 18 of pee. [00:38:00] And the patient’s heavily sedated. And I still have SATs that are, you know, in the seventies.

The first thing I would go to is a, a paralytic. Um, and then the next thing would be something like inhaled nitric oxide or, um, inhaled prostacyclin. And so I think physicians, uh, critical care physicians and intensivists that. Care for these patients have each sort of developed, you know, we have, we have a big toolkit of things that we can use as, um, in this bucket of like rescue modes.

Um, and I think people, you know, there’s, there really haven’t been a lot of studies showing that one thing is absolutely better than the other. And so we kind of use our clinical judgment and our experience and sort of pick, you know, the, the rescue modes that, that we think are most helpful. 

Nicole Kupchik: Okay. And then, I mean, that’s the thing is we just, we have very limited things we can do.

Right. Um, alright, so, um, extraoral membrane oxidation. So VV ecmo. 

Julie Bastarche, MD: Sure. ECMO is another great, um, therapy as a rescue [00:39:00] therapy. Um, that one is extremely invasive, as you know. I mean, that’s putting very, very large catheters into someone, um, to, to take blood outta their body, run it through an oxygenator and a CO2 scrubber and then put it back in the body.

Um, that is great in the right circumstance. Um. Not all hospitals have that. For example, my VA hospital, we don’t have ecmo. We’re fortunate we can send our patients, um, uh, to Vanderbilt across the street and have them get ecmo. Uh, the important thing with, um, ecmo, and we haven’t really talked about a RDS in the setting of multi-system organ dysfunction, but um, the lung is only one of the organs that.

That can fail. And so oftentimes we have patients who have really bad A RDS, but also their kidneys have failed. They’re in shock, and it looks like everything is shutting down in that circumstance, putting someone on s ECMO to rescue their lungs. Isn’t gonna help their other organs. [00:40:00] So ECMO is useful for someone who has, for example, COVID, A RDS, and none of their other organs have failed, and we just need to get their lungs over this, this hurdle.

So in a very select patient population, ECMO is a, is an excellent, um, an excellent option, but, uh, very invasive resource intensive and not available to everybody. I 

Nicole Kupchik: agree. It’s just, it’s, you know, in the ECMO centers that we do have often get overwhelmed, especially during like flu season and um, in certain times of the year, so, okay.

Alright, so let me ask you this question. I mean, we know lung injury is complicated. It’s extremely complicated in the setting of sepsis. So you’ve got, you’ve got a bird’s eye view on the clinical aspect of things, as well as the research aspects of things. So just if you think about the next 10 years, what makes you excited in just the research?

[00:41:00] Aspect of things that could possibly, we don’t know yet, but could possibly translate to the bedside? Like what gets you excited to like get up every day and go to work? 

Julie Bastarche, MD: Sure. So I think the, the, I think the, the biggest. Um, breakthrough that we’re gonna have in the next 10 years is really understanding all of the different diseases that make up, uh, a RDS and sepsis.

So I, I sort of use, um, I, I kind of think about cancer as an analogy. So, um, it used to be that we just had. Lung cancer. And then, um, we had, you know, we could then look under the, look at the cancer cells under the microscope and we had adenocarcinoma, squamous cell carcinoma, small cell, so we could differentiate the cancers by the, by looking at them under the microscope.

Now what we do is we have a lung cancer and adenocarcinoma. And we take a piece of that tumor and we send it to, uh, for genetic screening. And we [00:42:00] know that within that group of lung adenocarcinoma there are 10 or 12 different diseases. And that if we know exactly the mutation that is driving that lung cancer, we target that mutation.

We treat that lung cancer. So that’s what’s most exciting. We are, we are, uh, we are. On the cusp of doing that in sepsis and a RDS. So what we need to do is really, really, really take a deep dive into patients with sepsis and a RDS and multiorgan dysfunction syndrome. Study them very, very intensely by collecting biomarkers and, um, collecting clinical information and understanding the environment that they, they, um, live in and all of the factors that go into these.

Syndromes and in 10 years we’re not gonna be calling it sepsis. We’re gonna be calling it. Endothelial driven sepsis or immune activation, sepsis. Um, so we’re gonna have, we won’t [00:43:00] have sepsis anymore. We’ll have sub phenotypes or sub diseases in each one of those is, uh, once we understand the molecular mechanisms that drive it, we can then develop a targeted therapy.

So I think that’s what’s most exciting is our, our. The research community is poised to finally understand what sepsis is, and that’s gonna happen. I hopefully within the next 10 years, and then we can take all of the things that we’ve learned, um, in the laboratory from studying mice and cells and all of our experimental models and figure out which of those things we can use in which patients.

So I think it’s a really, really exciting time and for young people looking for. Career, uh, a research career or a clinical career? I think critical care is, um, we’re gonna see a lot of breakthroughs in the next 10 or 15 years. 

Nicole Kupchik: That’s super exciting. I’m, I love that you kind of set it up for everyone just to know like where research is going.

Um, ’cause it does make you excited to know that we can possibly improve outcomes at the bedside if we know what we’re [00:44:00] dealing with. So I just wanna thank you for being here today. I just, you know, I first of all go women in medicine. Um, absolutely love all the work that you’re doing and, um, and just, you know, thank you so much for sharing your knowledge and really all the dedication that you’ve given to medicine.

Julie Bastarche, MD: Thank you for the opportunity. This was, this was really fun. I had a great time. Thank you.

Nicole Kupchik: I hope you enjoyed the episode with Dr. Bastarache. I was honestly really excited to hear about a lot of the research, especially the research she’s involved in with GLP one drugs and really trying to figure out like, why do some patients get really sick with sepsis and end up with multiorgan dysfunction syndrome, and then why do others not?

And I, I just think it’s fascinating. Um. I’m really, really excited to know in the future to have a better understanding of what the answer to that [00:45:00] question is. So I just wanna thank her so much for all the work that she’s done and I, I really hope you’ve enjoyed this season of the sepsis spectrum. As we close out season two, I’m struck by how interconnected every story and system has truly been from the liver to the lungs.

The heart to the gut. A sepsis challenges every part of the body and every patient’s story reminds us what it takes to fight back. My hope is that these conversations have inspired a deeper understanding of not just the science of sepsis, but the resilience of those who survive it. Interviewing the amazing guests and hearing stories from patients that’s had a massive impact.

On me and my clinical practice, and I’m so excited to learn what impact it’s had on you. If you have a story you want me to read on the air next season, visit www.humancontent.com/sepsis. And if you’ve enjoyed the season of the sepsis spectrum, we [00:46:00] wanna hear about it. Please leave a review wherever you’re enjoying this podcast.

It truly helped. A ton. You can also reach me and our awesome team@infoatsepsis.org or visit sepsis podcast.org to share any stories of your own questions, concerns, or episode ideas. To learn more about Sepsis Alliance, visit sepsis dot. Org, the sepsis spectrum is brought to you by Sepsis Alliance. I’m your host, Nicole Kupchik.

Our executive producers are Allison Strickland, Hannah Sass, Claudia Orth, and Alex Colvin. Our producers are Aron Korney, Rob Goldman, Shahnti Brook, and me Nicole Kupchik. Our post-production producer is Sundus Hassan Nooli. Our editor and engineer is Jason Portizo, and our music is by Omer Ben-Zvi to learn about.

Sepsis Alliance’s podcast, legal disclaimer and compliance policies. You can visit sepsis podcast.org/disclaimers. The sepsis spectrum is a human content and sepsis alliance production.[00:47:00] 

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