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We sit down with pulmonary and critical care physicians Tonya Jagneaux and Hollis O’Neal to explore the complex challenges emergency departments face when diagnosing and treating sepsis. With overcrowded EDs, rising patient volumes, and strained resources, they discuss how new host response technologies are transforming early detection and treatment of sepsis, offering hope for better patient outcomes and more efficient care delivery.
Tonya Jagneaux and Hollis O’Neal are pulmonary and critical care physicians.
They discuss the KevinMD article, “The deadliest condition in emergency departments deserves a new diagnostic approach.”
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Transcript
Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome Tonya Jagneaux and Hollis O’Neal. Both are pulmonary and critical care physicians. The KevinMD article is “The Deadliest Condition in Emergency Departments Deserves a New Diagnostic Approach.” Tonya and Hollis, welcome to the show.
Tonya Jagneaux: Thank you, Kevin.
Hollis O’Neal: Thank you, Kevin. Great to be here. Thanks for having us.
Kevin Pho: So, Hollis, I’m going to start with you. Can you tell us the events that led you to write this collaborative article and then tell us what this article is about for those who didn’t get a chance to read it?
Hollis O’Neal: Sure. Yeah. So, you know, for, for years, for about the last 10 years, our hospital system and a group of physicians from LSU has been working in conjunction with a biotech company called Cytovale in developing a novel sepsis diagnostic.
And so we’ve been working with our providers, you know, critical care providers, I.D. providers, and kind of doing some of the preliminary work. Then in 2021, I did a multicentered study looking at this, you know, as a diagnostic test for sepsis and ultimately, in late 2022, it had an FDA clearance. Then in August of 2023, we implemented the test for use in our emergency department.
The way we did that was really a big combined effort between I.T., Dr. Jagneaux, our chief medical informatics officer. So, heavily kind of I.T.-based screening process for patients who walk into the door looking for signs or symptoms of infection. It’s a sepsis diagnostic, and so we want to be very clear about whom we actually applied the test to. Dr. Jagneaux was instrumental in developing that process and integrating this into the electronic health record.
It was also led by our quality department. Dr. Chris Thomas is one of our partners and the chief quality officer of our health system. In conjunction with our providers, we put this sepsis diagnostic into clinical use starting in August 2023. The test reports back a probability of sepsis, basically a low, intermediate, or high probability. We developed treatment pathways for that.
One of the things that happens is that for the high-risk population, what we call an interpretation band 3 result, that is a critical value that’s called back from the lab to the ED. We go find those patients and begin sepsis care right away. Some of those patients, you know, our ED is big and busy. We see 75,000 to 80,000 visits a year, at an 800-bed hospital. So big and busy. Lots of turnover of patients. Some of those patients are in the waiting room when the test comes back because Dr. Jagneaux had developed a process to order this at triage. Often, the result comes back before the doctor has even seen the patient.
When patients are in the waiting room, we physically retrieve them, bring them back. That obviously creates a resource drain on the ED because the reason they’re in the waiting room is there are no beds. So now we’re moving patients to the hallway and delivering care in nontraditional areas in the ED.
The question was, are we doing the right thing? When we identify these patients and pull them back, are we actually getting them back faster? Are they the right patients? Are these patients with sepsis? Are we delivering sepsis care to these patients faster?
The crux of this article was looking at that population of patients—those who were in the emergency department waiting room when the test came back. We physically retrieved them from the waiting room because they had a high-probability result. We found that the answer is yes to all of those questions.
First, we are getting them back faster. Patients with that band 3 high-probability result get back into the ED an hour faster than their counterparts. Second, are they sick? Yes. Ninety-plus percent of those patients are admitted to the hospital. Next, do they have infections? Yes, 90-plus percent of those patients have infections. Then, do they go on to develop sepsis? Yes, over 50 percent of those patients that we physically pull back from the waiting room will be discharged with a diagnosis of sepsis.
Ultimately, this told us that we are able to identify patients with occult sepsis using this rapid diagnostic. It’s a host-response tool, but we can find them when they don’t look that sick.
What does that mean? It means that a seasoned triage nurse sent that patient to the waiting room because they didn’t appear that sick. Their underlying biology says they are, but their overall clinical presentation says they’re not. We’re able to identify those patients, get them back, and deliver care more quickly.
Kevin Pho: So, before talking about this technology itself, Tonya, let me ask you: What are the traditional diagnostic approaches to sepsis, and what are some of the clinical limitations they have? What are the repercussions we currently have with traditional methods of diagnosing sepsis?
Tonya Jagneaux: Yes, I mean, pivotal to how the change management occurred with this test. Prior to that, as many physicians know, sepsis presents in varied ways. It’s complicated because of different patient presentations, as Hollis just described. Patients can look fine and be critically ill, or they can look critically ill and not have severe sepsis.
And we also, because of electronic health records, had this barrage of predictive tools and maybe sprinkled in there a few, you know, biologic tests that would offer some sense of maybe high risk. But I think the greatest challenge was the preexisting sepsis alerts that many hospitals had deployed—we had them as well. What they do is tell a story of maybe sepsis and generate actions that often result in alert fatigue or overutilization of resources.
We were in that mindset with both physicians and nurses, and there was a negative tone to sepsis alerts. If you mentioned that, most of the time, because they had experienced the low positive predictive value of those tests, it was almost as if there was no capacity to alert because they had been so overalerted. They had so much noise.
Now, we have this test that really brings promise. But we need to order it and ensure we find the right patient. The process to translate what was truly a biologic function into clinical bedside care was a critical piece. Medicine is always about discovery and improvement.
Alert science is interesting because people are hesitant to turn things off and miss something. But when you look at how traditional alerts perform, they also result in the inability to see anything relevant. This happens when you’re alerting all the time, not just about sepsis. Electronic health records offer a lot of alerting, creating challenges for the folks delivering bedside care.
We had to figure out how to highlight the needle in the haystack—those who truly needed attention. We also had to ensure we weren’t going down the wrong pathway with patients who might look critically ill but don’t have sepsis. Sometimes the default response was to assume it could be severe sepsis and implement the whole package: fluids, antibiotics, and so on.
So, yeah, that was the starting point. It required a dedicated approach. Thankfully, working with a great team, we were able to make progress. This is not just about deploying a test, making it available to order, and seeing what happens. There’s much more to it than that.
Kevin Pho: Tonya, just to follow up on that, to clarify: The current biomarkers we traditionally use for sepsis, like procalcitonin levels, don’t have the predictive accuracy you need to ensure the patient is on the right diagnostic path. Is that fair to say?
Tonya Jagneaux: Correct, yes. The ability of this test to decipher and provide better accuracy is much higher. Additionally, its negative predictive value is just as important. Being able to say, “No, this is not sepsis,” is equally vital to saying, “Yes, this is likely to be severe sepsis.”
Again, the challenge of sepsis is how varied it presents across the severity spectrum. The IntelliSep test has demonstrated an ability to parse that out. There’s a middle zone—a yellow category—but even that raises awareness that the risk for sepsis is higher than in the green category. For patients in the green category, we can reduce overutilization of antibiotics and fluids, providing comfort and confidence for providers.
This process allows us to better allocate resources, ensuring those in the waiting room who truly need a bed are prioritized. It’s not just about identifying sepsis but also about correcting diagnostics when it’s not sepsis. There’s true value in distinguishing between critical and noncritical patients, sepsis or not, moving forward.
Kevin Pho: Tonya, just to clarify further: If there is a delay in diagnosing sepsis, can you give us an idea of the clinical impact on a patient?
Tonya Jagneaux: There are a lot of numbers out there, but Hollis, correct me if I’m wrong: Every hour of delay increases mortality by about eight to 10 percent in the septic shock population. Traditionally, septic shock had a 40 to 60 percent mortality rate. It’s a time-sensitive disease.
We often talk about sepsis in the same way we discuss heart attacks or strokes. Time is muscle, time is brain, and in this case, time is life. Early antibiotics and fluid resuscitation improve survival rates and reduce morbidity. Delays can lead to prolonged hospitalizations, mechanical ventilation, deconditioning, and impaired recovery.
The full approach to sepsis care cannot be applied to everyone who looks septic by traditional SIRS criteria. Identifying patients during triage who need this test and having a process to highlight the results is crucial. If a high-risk patient is in the waiting room, someone must be aware and retrieve that patient.
Our triage process still uses traditional vital signs and logic embedded in the electronic health record. We ask about mental status changes, infections, and hypotension. When triggers are identified, we order specific labs, including IntelliSep, CBC, lactic acid, and chemistry panels. This initiates sepsis care and highlights potential cases for immediate attention.
Kevin Pho: So, Hollis, tell us about the technology behind this new diagnostic approach. You mentioned host-response technology. Briefly talk about the science behind it and why this new test works.
Hollis O’Neal: The science behind it is actually fascinating, and it’s elegant in its simplicity. The fundamental concept is one that’s intrinsic to all biology—structure and function are tightly related. If the function of a biological component changes, its structure often changes as well.
This test focuses on white blood cells, specifically neutrophils and monocytes. These cells are key players in innate immunity and are heavily involved in the sepsis response. When these cells are activated, their function shifts from a resting state to an aggressive, pathogen-detecting state. This functional shift is accompanied by structural changes, particularly in their nuclear architecture. For example, neutrophils can undergo a process called netosis, where they release their chromatin into circulation.
While these processes are beneficial at the site of infection, in the general circulation they can become pathological, causing microthrombosis, inflammation, and organ dysfunction. What this test does is detect these structural changes in white blood cells.
Using peripheral blood from a purple-top tube, the test applies microfluidics to expose white blood cells to hydrodynamic forces. High-speed cameras capture the cells’ response—watching tens of thousands of cells squeeze under these forces. A computer analyzes the video data and provides a score called the IntelliSep Index, ranging from 0.1 to 10.
The test divides the scores into three interpretation bands: low, intermediate, and high probability of sepsis. In our ED, we operationalize it using colors—green for low probability, yellow for intermediate, and red for high probability. These results are tied to specific actions to guide clinical decisions.
The process is quick and simple, requiring only 0.1 cc of blood. There’s no incubation or extensive preparation, and results are available within 10 minutes.
Kevin Pho: How accessible is this test? Is this something your institution is piloting, or is it available nationwide?
Hollis O’Neal: This test received FDA clearance in December 2022. We were the first health system to use it in our flagship hospital. It’s now implemented in all of the hospitals in our system, from smaller facilities with about 45 beds to our largest hospital with 850 beds.
We’ve already started to see improvements, including reductions in length of stay, costs, and mortality, particularly among patients in the low and intermediate bands. The results are promising, and as more institutions adopt this technology, we expect similar outcomes.
Cytovale, the company behind the test, is also working on securing broader insurance reimbursement. Currently, most tests roll into the hospital’s DRG because patients are typically admitted. Cytovale has a CPT code and is in discussions with payers to establish consistent reimbursement pathways.
Kevin Pho: We’re talking to Tonya Jagneaux and Hollis O’Neal, both pulmonary and critical care physicians. The KevinMD article is “The Deadliest Condition in Emergency Departments Deserves a New Diagnostic Approach.” Now, I’m going to ask each of you to end with some take-home messages for the KevinMD audience. Tonya, let’s start with you.
Tonya Jagneaux: It has been a pleasure to work with Hollis on this. I think it’s rare to witness such a breakthrough in the biology and diagnosis of sepsis. This is a significant step forward, not only in developing a test but also in pairing it with effective implementation science.
The lesson here is that any new medical innovation—no matter how promising—needs to be integrated thoughtfully. Implementation science is critical for ensuring that innovations reach the bedside in a cost-efficient and patient-centered way. It’s not just about creating the right technology but ensuring that it’s used correctly and effectively to benefit patients.
Kevin Pho: Hollis, we’ll end with you.
Hollis O’Neal: I think this process highlights the power of collaboration. When you bring together academicians, industry partners, and health systems in true partnership, innovation thrives.
This test is a perfect example of how a multidisciplinary approach can lead to better patient outcomes. It’s not just the test itself but how it’s integrated into workflows, from triage nurses to discharge planners. Every step of the process matters, and this level of teamwork is what drives success.
I also want to emphasize the role of our patients. During the research phase, we enrolled and consented patients walking into the ED with possible sepsis. These patients, despite being in distress, were willing to participate in research to improve care for future generations. Their contribution speaks volumes about the strength and resilience of our patient population.
If there’s one final message, it’s this: Innovation doesn’t stop at creating new tools. It’s about using those tools responsibly, collaboratively, and with the ultimate goal of improving patient care.
Kevin Pho: Tonya and Hollis, thank you so much for sharing your insights and perspectives, and thanks again for coming on the show.
Tonya Jagneaux: Thank you.
Hollis O’Neal: Thanks for having us. Really appreciate it.
