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Melanie Cole, MS (Host): Welcome to UF Health Med EdCast with UF Health Shands Hospital. I'm Melanie Cole. And today, as we talk about sepsis, participants will not only gain an in depth understanding of sepsis and its implications, but also cultivate the analytical skills necessary to navigate the ever-evolving landscape of sepsis knowledge and practice.

Melanie Cole, MS: Joining me, we have a panel with Dr. Philip Efron, he's the Director of the Sepsis and Critical Illness Research Center; and Dr. Nicole Iovine, she's a Clinical Professor and Hospital Epidemiologist, and they're both members of the medical staff at the University of Florida College of Medicine and UF Health Shands Hospital.

Doctors, thank you so much for joining us today. And Dr. Efron, I'd like to start with you. The burden of sepsis on our healthcare system is significant. Can you tell us a little bit about the current state of sepsis today, the prevalence, what's different now about what we know about this disease? Give us a little bit about how many people are affected each year and the critical implications within the medical field.

Philip Efron, MD: Absolutely. And thank you for having us today. That's a very important question. Just so the audience understands, sepsis is basically now defined as when your body has organ insufficiency after having an infection, so rather than just needing some antibiotics or feeling a little icky, your body tends to have an overwhelming reaction that can be very life-threatening. It is increasing in frequency and prevalence. This is for two reasons probably, or actually several reasons, not two.

Firstly, we're better at detecting it. We have improved awareness and people are knowing what to look for. So, what we in the past thought was some other disease, we're starting to realize is sepsis. Secondary, patient populations are changing. Sepsis can happen to anyone, but certainly is associated with certain types of individuals, such as those that are very young, those that are very old, immunosuppressed or cancer patients. And these patients are much more likely to be around in our current American society as well as other places around the world. I would say it's the number one most expensive condition in the hospital systems today. And most people don't realize that anywhere from one in four to one in five deaths in the hospital are directly attributable to sepsis or related in some way.

Finally, because we've gotten better at Identifying sepsis and using Surviving Sepsis guidelines put out by many national societies, we're able to intervene and keep people alive. Many people actually still don't do very well after one to two years. And similar to patients that may have a stroke or when you've heard about post-ICU syndrome or long COVID, these are issues that can be related long term to cognition, frailty as well as repeat infections and potentially passing away rather than sort of getting back to normal. So, it is a huge burden currently on our society.

Nicole Iovine, MD: I would like to add also part of the contributing factors also include really what we do to patients. We have so many advanced modalities now that, you know, were available in years past, but these things can put patients at greater risk for infection. So, we have all sorts of monoclonal antibodies to treat inflammatory diseases; we have cancer chemotherapeutics that are also antibody-based; and also just the simple fact of putting lines in patients, central lines; also, patients with heart failure, having LVADs, all of these things. It's like a double-edged sword. We need them, we have to have them, but they present risks which can manifest as sepsis.

Melanie Cole, MS: Thank you both for that. And Dr. Iovine, as we're getting this comprehensive understanding of sepsis and acknowledging that multifaceted nature of the risk assessment. And Dr. Efron mentioned a little bit about risk and that it's grown over the years to a bigger, broader range of people. I'd like you to speak about identifying individuals who might be most susceptible to this life-threatening condition. When they're in the hospital, you mentioned a few things, lines and some other things, but if we're looking at identifying these individuals for risk assessment when they're in the hospital, what would you like other providers across the spectrum of healthcare providers that are working with these patients to be on the lookout for?

Nicole Iovine, MD: Yes, that's a wonderful question. So, what we teach our providers are to think about sepsis when they're evaluating a patient for whatever reason it is. So for example, you have a diabetic who comes into the hospital, they haven't been taking their insulin, and you're thinking, "Oh, this patient is in diabetic ketoacidosis," which they might be, but we teach our providers to think, "But is this sepsis also?" So, having a high index of suspicion at all times is really what is really important to capturing sepsis because we know sepsis can be insidious, it develops over time, it can creep up on you. So again, to use that same example, you know, the patient may be coming in with diabetic ketoacidosis, but sepsis is already brewing in them. So, even though you clinched it, you're like, "They're in DKA," you still have to think, "Okay, so maybe the patient's not getting better as quickly as I think. Why could that be?" So, we teach our providers to think sepsis.

Melanie Cole, MS: What does that mean, Dr. Iovine, to think sepsis? What are we actually looking for if they're working with someone with DKA, then what does think sepsis actually mean?

Nicole Iovine, MD: So when people are presenting acutely, of course, you know, your differential is going to be broad as it should be. But as time goes on, you hone your diagnosis. But if you're in a situation where you're like, "Oh, okay, I'm treating whether it's a cardiogenic shock or it's DKA," but some things are not fitting. So for example, the DKA patient who is spiking a fever, that would say, "Hey, why is that happening? That's not what I typically see when I have my DKA patients." So I would say that what we're trying to get our providers to do is that not to have what we call an anchoring bias that we figured out that they have condition X, and that's all condition X could be, to continue to re-evaluate, reassess data as it comes in, the symptoms of the patient as well as the laboratory and imaging data that you're getting and not to dismiss the outliers, but think to yourself, "Okay, this isn't fitting with what I initially thought." Think broadly and think about could sepsis be causing this. Could sepsis be the reason for this fever? Or maybe that is an infiltrate on that chest x-ray. Maybe pneumonia is present here as well, and could that be causing sepsis? That's what I'm talking about.

Philip Efron, MD: I would like to agree with everything Nicole said, and would like to add that it's still unclear to many providers as to how sepsis could be causing what's going on. In different patient populations, it can often show up in different ways. For instance, as Nicole had been mentioning, you can have altered mental status. Now, appropriately, people may consider this a stroke, and that should be ruled out. But at the same time, this is frequently how sepsis can show up in the older population. This is also true for certain heart arrhythmias, atrial fibrillation in the intensive care unit. Again, cardiac causes must be ruled out, but frequently this can be sepsis.

So by getting the word out there for people to understand what sepsis can do, how it shows up in different ways, is very important, especially because, like other key conditions, whether it's hemorrhagic shock where you're bleeding to death, a new heart attack, or a stroke, time is money and time is life. The sooner that you are treated appropriately, which usually involves things such as antibiotics, volume resuscitation, and potentially some other what we call source control maneuvers, the much better chance you have of surviving. The longer you wait, the worse your outcomes will be.

Melanie Cole, MS: Well, then Dr. Efron, as we're looking to optimize a patient's chance of survival here synthesize for us some recent advancements in diagnosis because we've heard about some biomarkers to facilitate diagnosis. Is there anything you would like other providers to know about so that they can ensure a good diagnosis of this and start the treatment timely?

Philip Efron, MD: I would say, and again, as Nicole had mentioned earlier, that still at this time, the most important thing is to be acutely and hyper-aware and suspect sepsis. There are biomarkers that are coming out. There are other tests that people are doing and some of them seem very promising. But at this time, I couldn't tell providers that this is something you should use 100% of the time, you know, for your practice. I think that by looking at the Surviving Sepsis guidelines, following some of the information that's put out by specific societies on recommendations on what to do and tests to order. I think, including the government, so CMS, Medicare, Medicaid, have tried to make it very clear what would be a good pathway when you suspect sepsis to do for things. And I will say under Dr. Iovine's leadership here at UF, they've made it, I wouldn't say simple, but they've really enabled the staff here, when they suspect sepsis, to be able to get it right. And that includes efficiently allowing labs and things to be done and having the staff all sort of come to the bedside for sepsis alerts so that the patient can be treated in a rapid manner.

Nicole Iovine, MD: I think that what you're getting at also, Dr. Efron, is that sepsis is a syndrome. There is no single lab test, there is no single imaging, there is no single one thing that will say, "Yes, this patient has sepsis." And just to make a simple contrast, if you're thinking that perhaps your patient, let's say, has a urinary tract infection, you send a urine culture, and when it comes back, then you can tell if there is a urinary tract infection. But with sepsis, it being a syndrome, and it presenting in so many different ways, really, you have to look at the whole constellation of what is going on. There are some lab values that help you. One of them would be the lactic acid level. An elevated lactic acid level is present during sepsis. But it's present during many other things as well, so you can't just use that. We look at procalcitonin as an indication of whether or not infection is present. But again, that is not the only piece of the story. We look at laboratory values. And also, as Dr. Efron mentioned, we look at the mental status of the patient. So, you really have to look at all of these things and integrate them to determine if a patient is at risk of sepsis or is in fact septic.

Melanie Cole, MS: Well, then Dr. Iovine, I'd like you to speak about treatment recommendations, how they differ in the acute and less acute phases of treating it. But so that if it's caught in these early stages, what are some of the key recommendations for practice for the clinical practice guidelines for management? What are we doing as far as antibiotic selection? What are you doing for them?

Nicole Iovine, MD: So, there's a lot of activity, that has to happen within the first hour. They call it the One-hour Bundle. And it includes things like getting your blood cultures before you give the antibiotics, because, obviously, if you give the antibiotics first, then you're going not have an informative blood culture. If the patient is in shock, fluid resuscitation. And if the patient is in shock that's not responsive to the fluid, we have to start vasopressors. So, there's a lot of activity early on when you've identified a patient as being septic. But very key parameters of it would include getting those blood cultures, getting antibiotics started and fluid resuscitation.

Now, the antibiotics that are typically used, is we try to cover for a class of bacteria known as gram-negative bacteria. So usually, you end up using a class of antibiotics in the cephalosporin family, so that could be ceftriaxone. Oftentimes vancomycin is added to cover the gram-positive agents, but that is not necessarily always required. Certainly if somebody has lines and something that breaches the skin integrity, then that would be a very classic example of why you might want to cover gram-positive bacteria with vancomycin. But certainly, having your cephalosporin on board as quickly as possible right after you draw those blood cultures is very important.

Philip Efron, MD: I would like to add that another key aspect is to have a multidisciplinary approach in most sepsis, except for potentially pneumonia, requires additional interventions to be done for something we call source control. If the sepsis is related to a foreign body or some sort of catheter, it needs to be removed or replaced. If the sepsis is due to some sort of abdominal issue, then usually some sort of intervention, whether it's a drain or an operation will need to be required to have the patient recover. So as Nicole mentioned, the key is that first hour, but your job isn't done and that's sort of why the government insists that before six hours, you have a subsequent followup where you see if the patient's getting better or worse and you've determined exactly the sort of care that needs to be done, which may include being moved to a more intensive care unit, either an IMC or an ICU, to allow better supervision and treatment of the patient.

Melanie Cole, MS: I'd like to give you each a chance for a final thought. And Dr. Efron, I'd like you to expand a little, you mentioned multidisciplinary approach. I'd like you to speak about UF Health's multidisciplinary initiatives that are aimed at addressing sepsis and how collaborating research endeavors are working to hopefully tackle this particular situation and some of the quality improvement initiatives and educational programs aimed at sepsis awareness.

Philip Efron, MD: That's a great question. So, I would say that UF Shands has taken this very seriously. And this includes, not only sepsis committees, but education that goes out to all trainees, as well as all staff regarding best approaches to sepsis and how we can intervene appropriately to make sure that people's loved ones do better or go home. I would say that Nicole can probably better answer some of the other Shands efforts that are specifically out there and how we make sure this happens. In fact, we have a meeting this afternoon to discuss more about what we've been trying to accomplish for the past several years to improve sepsis outcomes at the University of Florida in Shands.

I will say that I'm very proud of the work that our Sepsis and Critical Illness Research Center has been doing here at UF to sort of work alongside our clinical colleagues to improve outcomes. We have taken a significant interest in trying to determine why patients do or do not get better after the initial insult. So, we work with everyone, of course, to do what's best clinically. But after that, there's an important aspect of precision and personalized medicine that is going to be required to treat individuals. As we found from previous experiments and research in the past, there's no silver bullet to sepsis. As Nicole mentioned, this is a syndrome. And each individual may or may not require this intervention at this time with this drug. So, we have been working hard with government funding to sort of determine who needs what, when, and why. And that's sort of some of our ongoing efforts currently to sort of determine how best to get patients better back to normal. Return them to the homeostasis where they were, which is usually walking and talking before sort of all this sort of occurred.

Melanie Cole, MS: Dr. Iovine, last word to you, expand on what Dr. Efron was speaking about, about some of the initiatives and what you would like other providers to take away from this very important topic today.

Nicole Iovine, MD: Yes, Thank you. I would expand upon Dr. Efron's emphasis on the teamwork that is necessary. And the teamwork can be the team that's at the bedside taking care of the patient. That is extremely important. You have respiratory therapy, you have the nurses, you have the physicians, you have the physician assistants, you have imaging. But I would also want to take another maybe a 30,000-foot view because the team really has to span the entire institution. So just as one example, because here at UF Health, we take sepsis extremely seriously, we have the resources; therefore, because our senior leadership recognizes it's important, that we can also look at our data and look at it.

We have a number of quality specialists who will parse the data for us so that we can really dive into it and see, "Well, you know, we started doing things this way. Is that working? Is it not working? Is it helping or not?" And that is so very, very important, is that you need to always reflect back and look to see what we're doing here as an institution, is this adding value? Is this helping improve the quality and safety of our patients. And that is extremely important to do on a continual basis. So, that kind of larger quality infrastructure is also really important to support our teams at the bedside and make sure that what we are doing is really making an impact.

Melanie Cole, MS: Thank you both so much for joining us and sharing your incredible expertise on sepsis for other providers. To learn more, please visit scirc.med.ufl.edu or to learn more about other healthcare topics at UF Health Shands Hospital, please visit innovation.ufhealth.org. That concludes today's episode of UF Health Med EdCast with UF Health Shands Hospital. I'm Melanie Cole. Thanks so much for joining us today.