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Dr Rania Habib (Host): The CDC estimates that at least 1.7 million adults in the US develop sepsis each year, and 87% of cases start before the patient even makes it to the hospital. This is Expert Insights with the Carle Foundation Hospital. I am your host, Dr. Rania Habib. Today's guest is Dr. Benjamin Davis, the Associate Medical Director of Emergency Medicine, and he is here to discuss the diagnosis and management of sepsis. Welcome, Dr. Davis.

Dr Benjamin Davis: Hey, thanks for having me.

Host: So, the incidence of sepsis in the US is staggering. And as an emergency medicine physician, you are often the first line in diagnosis, so we welcome your expertise on this topic. Could you please review the definition of sepsis?

Dr Benjamin Davis: So generally speaking, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Practically speaking, how do you diagnose it? That's a difficult thing. And so, the definition that is currently used by CMS, and it's not without some controversy, is the presence of infection plus the presence of two out of four SIRS criteria, systemic inflammatory response syndrome criteria. And those criteria are a temperature of 38 Celsius or below 36; a heart rate greater than 90, a respiratory rate greater than 20 or an elevated white blood count or a low white blood count. So, those are the four SIRS criteria.

Host: So, what causes sepsis?

Dr Benjamin Davis: That's part of what makes things difficult. So, sepsis as a term has been around for a thousand years and it is going to be typically caused by bacterial infection. Although truly the syndrome of sepsis, so something that causes this whole body response leading to organ dysfunction and leading to these criteria, the SIRS criteria, can be caused by other things as well, can be caused by fungal infections, viral infections. But we typically think of it as a bacterial disease and the emphasis is on treatment of bacterial sepsis. So, I think that's the most useful way to think about it. What we're talking about is bacterial infections.

Host: And are there specific strains of bacteria that you see more often lead to sepsis compared to others?

Dr Benjamin Davis: Really, any bacterial infection that we commonly see can certainly lead to sepsis. And so, Gram-negative organisms tend to be a little more, but even our staph and strep can definitely cause strep can cause sepsis frequently in hospitalized patients. Patients that are at higher risk are going to be your immunocompromised patients either due to underlying medical problems or due to treatments for underlying medical problems like chemotherapy for cancer, for instance, is frequently going to lead to an immunocompromised state, which would make you higher risk of sepsis.

Host: What are some of the main signs and symptoms that you often see in the emergency room that lead you to develop a working diagnosis of sepsis?

Dr Benjamin Davis: The big things would be these SIRS criteria. We look for the presence of fever, for one, or hypothermia. And then, it's looking for these abnormal vital signs. And in emergency medicine, we're always on the lookout for those. And of course, other things can cause you to have an elevated heart rate or elevated respiratory rate. Trauma or pancreatitis or some other surgical problem may cause those things as well. So, we're first looking screening patients for, "Do they have any of these criteria?" And then, "Do we think that they have an infection?" And so, we actually have our nurses, even at triage when they're first encountering the patient, they are alerted if a patient meets two out of four SIRS criteria. And then, they will be inputting, "Do I think that this patient might have an infection?" And if they meet all those criteria, then that causes an alert that then will be reviewed by the provider who will decide, "Okay," and actually initiates some orders just from the triage nurse and then it alerts the provider that those are in process.

Host: That's fantastic that you already have those elements streamlined in the emergency room. So, what tests are you running as a provider that helps you confirm the diagnosis of sepsis in addition to those criteria that you're already using from the observation?

Dr Benjamin Davis: We're running a lot of tests. It is difficult and it's time-sensitive. So, we would get general blood tests, a complete blood count, because the white blood count is one of those SIRS criteria, and that's something that we're not going to have when the patient first arrives most of the time, unless they had had lab work previously. So, they're going to get a complete blood count, they'll get a metabolic profile; a lactate level, lactic acid level, it has some correlation with severity of sepsis, so we check that. And then, blood cultures, which don't provide us immediate information, but that is helpful once the culture's result, which is typically going to be 24 hours or longer, then it can guide therapy and help to confirm the diagnosis. However, you can still have sepsis without having a positive blood culture.

Host: So when you're seeing this patient in the emergency room, what are your priorities in the initial management of a patient that you have confirmed or you're on the way to confirm that diagnosis of sepsis?

Dr Benjamin Davis: So, the number one and overarching priority is to get appropriate antibiotics on board in the patient in as timely a fashion as possible, so as soon as possible. And that's particularly true for patients who really have the severe sepsis or septic shock where their tissues are fused and they are at high risk of mortality. So, the overarching goal is to get those antibiotics on board as soon as possible. And our goal is to do that in less than an hour from arrival in those septic shock patients. So, that's priority number one.

We also focus on resuscitation. So, fluid resuscitation is an important thing as well. If the patient's hemodynamics are abnormal, then fluids would be the initial step to trying to address that. And so as far as treatments, the initial treatment's going to really be focused on antibiotics and then appropriate fluid resuscitation. And other resuscitation are usual critical care kind of skills. Does the patient need supplemental oxygen? Do they need non-invasive ventilatory or support? Or do they even need to be put on a ventilator? Do they require pressors to keep their blood pressure up, which may be initiated early on as well?

Host: What are your current main options for the antibiotics when you're deciding to start them within that hour?

Dr Benjamin Davis: So, we have built within our sepsis order set, there is an antibiotic based on local resistance patterns and antibiotic stewardship here at Carle for your suspected source of infection. There is at least two choices of antibiotics for each suspected source. And it would typically be one that's going to be maybe beta-lactam-based, and then one for somebody who has a penicillin allergy. And so, for each suspected source, it gives typically a broad-spectrum initial option because given that we're not going to be completely certain what antibiotic we want, we want the initial antibiotic to be fairly broad-spectrum. However, depending on risk factors and depending on your suspected source, there may be additional antibiotics that are going to be considered. For example, that immunocompromised patient, we're going to want MRSA coverage as well, so typically a vancomycin or something similar and also want to have pseudomona coverage. So, you're going to get at least one antibiotic with anti-pseudomonal coverage.

Host: Could you discuss some of the controversies that exist in the management of sepsis?

Dr Benjamin Davis: There are several. One is on diagnosis, that I mentioned the importance with these septic shock patients, that's really where we want to focus. Unfortunately, there are a huge number of patients that will meet the SIRS criteria. And so, many of them, it may not be clear early in the course whether or not they have an infection. So, it may be difficult to ascertain in the emergency department, does this patient really have an infection or not? Certainly with the septic shock patients who are really critically ill, we can take an approach of if we give them a dose of antibiotics and ultimately we find out they have pancreatitis instead, and there's not an infection here, we're okay with them getting a dose of antibiotics.

On the other hand, if we take a huge population and give them unnecessary antibiotics, that can be harmful, right? So, we want to be good stewards of antibiotics. And so, one controversy that the Infectious Disease Society of America has questioned, "Do we want to focus on all septic patients? Should we just be focusing on septic shock patients?" A more stable patient, we can wait and take a little bit more time. And, you know, maybe it's okay if it's six hours from now that we decide, "You know what, we're going to give antibiotics." Whereas currently, it's much more broad to get those antibiotics on board early in all of these patients. So, that would be one thing.

I mentioned fluid resuscitation. That's something that there was a recent study in the New England Journal within the past couple months, calling into question the benefit of aggressive. What's currently recommended is that unless the patient has a contraindication, they get 30 milliliters per kilogram of crystalloids. And so, that can be a lot of fluid for a lot of patients. And there's evidence that that may be harmful even to patients who don't have obvious contraindication. And the recent study showed that there was really no difference in a more conservative approach to fluid administration in sepsis versus that very aggressive 30 per kilo. So, that may be something that we see as additional studies come forward and the guidelines may change to reflect that, that we're not as aggressive with fluids upfront as we are currently.

Host: That definitely makes sense, especially with that high value of the resuscitation fluid volume compared to, you know, your normal fluid volume. So for those patients that you're worried about potential fluid overload, how are you managing that with that criteria of saying, "Okay, we should consider a higher volume?"

Dr Benjamin Davis: We certainly are aware and don't give a patient who has a severe cardiomyopathy, for example, congestive heart failure, and we know their ejection fraction's 10%, we don't give them that 30 per kilo just as a blanket order, that that patient's going to be resuscitated with fluids much more carefully with small, kind of stepwise bolus of the fluid. But it is tricky, and it's also tricky because this is something that we try to, from a quality standpoint, monitor very closely. And so, it does require making sure you've documented, "Okay, why did you not give the fluids?" And I think that seeing that in the future maybe be a little more patient-specific, where we're given the providers a little more latitude in terms of using their clinical judgment surrounding the fluid resuscitation will be beneficial.

Host: Absolutely. And how are you in the emergency room making that handoff between the patient who has septic shock? And, let's say, the higher level care of ICU, what's the time priority in getting that patient to the ICU?

Dr Benjamin Davis: As soon as we know that that patient is going to need ICU level care, we notify our ICU colleagues. We are going to continue the resuscitation as we have, and that may include initiation of vasopressors, especially if the patient's already received the fluid resuscitation that's appropriate for them. And so, we're fortunate here that our ICU colleagues are very good and aggressive with getting patients up to the ICU pretty quickly. There are other EDs across the country where ICU patients may board in the ED for a long amount of time. That does not happen here very often. In fact, it's been a long, long time since we've had anybody down here for a long time. But when that happens, they come to the ED, they're at the bedside, we're working together and we discuss it as a team and have a plan. So, it's really, really pretty smooth.

Host: That's wonderful. The CDC estimates that one in three people who dies in a hospital actually had developed sepsis sometime during that hospitalization. And they also suggest that up to 87% of those cases had sepsis before they even made it to the hospital. So obviously, sepsis management is extremely important. What do you anticipate will be the future direction of management?

Dr Benjamin Davis: So, I think that the current paradigm, which really goes back, it's kind of my career has gone right along with it, if we look back at the modern sepsis care, Manny Rivers' 2001 article on Early Goal-Directed Therapy was sort of the nidus for this. So, I think we've evolved and refined over that 20-year period. So, I don't think there's gonna be a dramatic change. I think you're just going to see further refinement of how we do things and probably better delineation of the fluids like we talked about. But I think even with antibiotics and timing of antibiotics, that we will hopefully continue to get better at identifying patients. And I think that there's a lot of work either through broad assessment of biomarkers or even just patient data from the electronic medical record using artificial intelligence to identify that, theoretically, you could look at a patient with these characteristics on these medications with these diagnoses, who presents with these vital signs, this is this percent chance of being sepsis. So, I think we will get much better at identifying and having a better idea of which patients are at risk than we even do right now.

Host: We would welcome that opportunity. Well, thank you so much for your time, Dr. Davis. Would you like to add any key points for our listeners?

Dr Benjamin Davis: As I mentioned before, that the primary key point is just getting those early antibiotics on board, especially in our septic shock patients. And we've worked hard to have a protocolized approach to how we manage sepsis as many EDs have. And I think that's very helpful and really key to being able to give these patients the best care.

Host: Absolutely. And as a surgeon, you know, I appreciate all the information that you've provided because I certainly refer my patients who I am really worried about sepsis to the emergency room as soon as possible to try to prevent that progression to septic shock. So, we definitely appreciate everything that you and your colleagues do the in the emergency department.

Dr Benjamin Davis: Awesome. I appreciate that. We appreciate you as well.

Host: For more information and to get connected with one of our providers, please visit carle.org. Or for a listing of Carle providers and to view Carle-sponsored educational activities, head on over to our website at carleconnect.com. That wraps up this episode of Expert Insights with the Carle Foundation Hospital. I am your host, Dr. Rania Habib, wishing you well.