Ep. 194: Reducing Risk and Improving Care for Pediatric Sepsis

One in five pediatric hospital deaths is linked to sepsis — a statistic that has driven decades of research and is now reshaping clinical guidelines worldwide. With the 2026 enhanced guidelines just published, there's no better time to dig into what the science is telling us. We're joined by Scott L. Weiss, MD, MSCE, Division Chief of Critical Care Medicine and Vice-Chair for Research at Nemours Children's Health — and co-author of both the 2020 and 2026 guidelines — to walk us through the research building a clearer, more consistent approach to recognizing and treating pediatric sepsis, and what it means for children and the clinicians who care for them.

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Featuring: 
Scott L. Weiss, MD, MSCE, Division Chief, Critical Care Medicine; Vice‑Chair for Research, Department of Pediatrics, Nemours Children’s Health

Host/Producer: Carol Vassar

Views expressed by guests do not necessarily reflect the views of the host or management. 

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Announcer (00:00):

Welcome to Well Beyond Medicine, the world's top-ranked children's health podcast, produced by Nemours Children's Health. Subscribe on any platform at nemourswellbeyond.org or find us on YouTube.

Carol Vassar, podcast host/producer (00:12):

Each week we'll be joined by innovators and experts from around the world, exploring anything and everything related to the 85% of child health impacts that occur outside the doctor's office.

(00:24):

I'm your host, Carol Vassar. And now that you're here, let's go.

MUSIC (00:30):

Let's go, oh, oh, well beyond medicine.

Carol Vassar, podcast host/producer (00:36):

Hey everyone. We are in Boston, Massachusetts. We're at the Pediatric Academic Societies meeting 2026, and with me right now is Dr. Scott Weiss, who is insisting that I call him Scott.

(00:49):

Scott, welcome to the podcast.

Scott Weiss, MD, Nemours Children's Health (00:51):

Thank you. It's great to be here.

Carol Vassar, podcast host/producer (00:52):

We are here to talk about this momentous year that you're having. It's only April as we record this. We're going to release it in May. But so far, you have been published in JAMA. You're about to be published as of this conference in the New England Journal of Medicine. And you have led the International Surviving Sepsis Campaign Guidelines for Children, the update from 2020, which is new in 2026.

(01:19):

Sepsis research, sepsis treatment is really your bailiwick. Tell us what sepsis is from a very high level, and also septic shock, because we're going to get into that a little bit later.

Scott Weiss, MD, Nemours Children's Health (01:32):

Sure. So sepsis is formally defined as a dysregulated host response to an infection that results in life-threatening organ dysfunction. What that actually means from a practical standpoint is a really bad inflammatory response to an infection that results in multiple organ systems failing. It can come on very suddenly and make children and adults very sick very quickly. Septic shock is the most severe form that involves cardiovascular dysfunction. Most often a decrease in blood pressure where the body has trouble delivering oxygen and other substrates in the blood to the organ systems to function properly.

Carol Vassar, podcast host/producer(02:15):

Are kids particularly vulnerable? I think there was a stat in one of your studies that said one in five hospital deaths of children can be associated with sepsis or septic shock. Is that true?

Scott Weiss, MD, Nemours Children's Health (02:29):

Yeah, that's what our most recent epidemiological study was able to demonstrate. So in 2024, I was part of a panel led by the Society of Critical Care Medicine or the Task Force of the Society of Critical Care Medicine that redefined criteria for sepsis. And so the focus of our recent JAMA publication was identifying the epidemiology of those new criteria to identify children with sepsis across the United States. And so what we found was that there's roughly 18,000 cases of sepsis in children throughout the United States each year, and one in five hospitalizations that ends in death involves an episode of sepsis.

Carol Vassar, podcast host/producer (03:15):

One of the unique identifiers of this or differentiators of this particular JAMA study was that you didn't look at billing data. You looked at EHR data specifically from, I think it's HCA Healthcare and from Epic Cosmos. How did that make a difference in what you determined?

Scott Weiss, MD, Nemours Children's Health (03:38):

Yeah. So we live in a digital world, obviously. And now, fortunately, most healthcare data is electronic. And so we were able to take advantage of that to go right to the direct source of the electronic health record to identify the elements that we can put together into the criteria that meet the definition of sepsis. And so that has specific advantages compared to billing data.

(04:12):

So, billing data is the result of somebody interpreting clinical data and applying a category of medical problem to that data. And so there's a lot of variability and inconsistency. That's a problem when you're trying to follow epidemiological trends over time as well as benchmark outcomes and treatment between hospitals. And so by utilizing the direct data within the electronic health record, we can come up with an objective, reliable, and consistent way to identify sepsis that doesn't rely on subjectivity inherent within individual sites.

Carol Vassar, podcast host/producer (05:00):

Did this show you that the issue is possibly larger than you had and other researchers had thought?

Scott Weiss, MD, Nemours Children's Health (05:10):

That's a great question, and it depends a little bit on perspective. Because there's no gold standard criteria to diagnose sepsis and it relies on the combination of multiple different clinical elements, there's many different ways that you can identify cases of sepsis. And so estimates in the United States have ranged from a few thousand to 100,000 kids per year. But what was important with this work is that we applied what is now accepted as the most up-to-date criteria, operational criteria, to identify sepsis so that everyone's talking about the same exact thing as opposed to one group talking about one set of criteria and a different group talking about a different set of criteria. Now we're all on the same page in terms of how many children we have in the United States who have a very clear set of criteria, who could be identified for research studies, who we can follow for quality improvement initiatives, who we can take for public policy and advocacy for example. So it's helpful to have one set of common criteria we apply to all of those different domains.

Carol Vassar, podcast host/producer (06:25):

You're finally comparing apps to apples, if you will.

Scott Weiss, MD, Nemours Children's Health (06:27):

Exactly. That's right.

Carol Vassar, podcast host/producer (06:29):

I want to get to your New England Journal of Medicine study, your trial, but first I want to talk... Since we're talking about criteria, you have done some work internationally, the 2026 International Surviving Sepsis Campaign Guidelines for Children. What's that all about?

Scott Weiss, MD, Nemours Children's Health (06:49):

So the Surviving Sepsis Campaign was started as a collaboration in the early 2000s between the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, mostly focused at that point on adult sepsis, but as a way to bring together experts from across the world to look at the available evidence in a comprehensive way and provide practical guidelines for clinicians. There's so much that goes into recognizing and taking care of a patient with sepsis that it's very difficult for any individual clinician to have the best data and the most up-to-date evidence at their fingertips at any one point. And so the Surviving Sepsis Campaign was focused on doing that.

(07:34):

It's been incredibly successful with reducing mortality in adult sepsis. And so in 2020, we were able to apply that methodology for the first time to come to produce pediatric- specific guidelines. And so the 2026 publication was an update based on the latest evidence for how we should be recognizing and managing children with sepsis and septic shock across the world.

Carol Vassar, podcast host/producer (08:00):

What's different from 2020 to now in the guidelines?

Scott Weiss, MD, Nemours Children's Health (08:04):

So there's been several updates that I think are really important. First is what we saw from the 2020 guidelines was that there was not a lot of studies that met the threshold for high certainty of evidence.

Carol Vassar, podcast host/producer (08:22):

Okay.

Scott Weiss, MD, Nemours Children's Health (08:23):

As part of that effort, the panel identified over 50 research gaps. And now some of those gaps have been addressed. One example is the New England Journal trial that we did, looking at different fluid types. Unfortunately, that was not ready to be incorporated into the evidence for the current guidelines, but other studies have. For example, in the United Kingdom, researchers identified that excessive oxygen delivery is actually associated with harm. And so previously it was recommended to give high levels of supplemental oxygen to children with septic shock because we know that deficiencies in oxygen delivery at the tissues is a big part of the pathophysiology of sepsis. However, that trial showed that that is helpful to a point but can become harmful if you overdo it.

(09:16):

So we learned a lot from the 2020 effort in terms of new studies and new guidelines. But some of the key guidelines that are incorporated into 2026 were really a focus on having a comprehensive sepsis program at your institution that can track the patients you have with sepsis and look for opportunities for improvement. I think the epidemiological study from JAMA provides a toolkit now for hospitals to be able to do that in a reliable and consistent manner.

(09:49):

The new guidelines also focused on some of the newer efforts around immune modulation, which is really important given that sepsis is fundamentally a problem of a dysregulated immune response. Unfortunately, there was not sufficient evidence to provide a lot of guidance to clinicians in terms of what they should do now, but I'm hopeful that identifying knowledge gaps will again trigger new studies that will help us in the future.

(10:19):

And then lastly, the new guidelines incorporated the need to identify children at risk for long-term problems. We know that most of our children who develop sepsis do survive, which is great news, but we know up to 30 to 40% of them will suffer long-term neurobehavioral and cognitive morbidities. And the new guidelines provide criteria for screening and following those patients so that we can continue to improve outcomes even for those who survive sepsis and are able to leave the hospital.

Carol Vassar, podcast host/producer (10:54):

You mentioned a word, screenings. Is there a standard screening for identifying sepsis in the clinical setting?

Scott Weiss, MD, Nemours Children's Health (11:04):

So screening for sepsis was something that got a lot of traction about 10 to 15 years ago. And the guidelines around that time were really emphasizing some sort of screening tool to help clinicians recognize sepsis early. Unfortunately, one of the biggest risk factors for poor outcomes is not being recognized with having sepsis early enough. And so a variety of screening tools have been tested and implemented, and have been very, very helpful and effective.

(11:38):

The newer evidence is a little less clear about whether some of those screening tools are still necessary because there's been so much education and work done to help clinicians recognize sepsis in a variety of ways that in some systems, in some settings, screening tools don't add much more. However, there are still healthcare systems where having that safety net of a screening tool to help flag and support clinicians in recognizing sepsis early is still very important. I think the trick now is to work with your local system to figure out whether that is helpful for your clinicians at your facility, at your place. And so I think that's where some of the controversy comes into place. I think there are some systems where a screening tool doesn't add much, but there are some places where it still can be very, very important to help early recognition of sepsis.

Carol Vassar, podcast host/producer (12:36):

Where do you fall on that spectrum?

Scott Weiss, MD, Nemours Children's Health (12:39):

So we at Nemours developed a screening tool called the Nemours Shock Score about 15 years ago and have had a lot of success with that program. When it was last studied about seven or eight years ago, we found that two-thirds of kids who triggered an elevated shock score that brought providers to the bedside had a new intervention related to that screening alert. And so at that time, it did seem to be very helpful and effective. Anecdotally, I do think that it's helpful in some cases, but we're now actually launching a new study to determine whether or not our shock huddle is still helping clinicians the same way it was in the past and to maybe identify opportunities to tweak the process so that we continue to get the most out of it.

Carol Vassar, podcast host/producer (13:30):

Continuous improvement through quality and safety, and-

Scott Weiss, MD, Nemours Children's Health (13:32):

Exactly. Right.

Carol Vassar, podcast host/producer (13:33):

... looking at the system and seeing where you can improve it. Let's get to the piece. To resistance. My French is terrible. The PRoMPT BOLUS trial, that's a lot of people here, or PAS are so excited about this. If I'm understanding this correctly, and I'm not a clinician, the study focuses on what kind of fluid is given to a child, and we're talking specifically about septic shock. Is it going to be the 0.9% saline? Is it going to be something that's more aimed at the body's own chemistry? This is fascinating work. Tell me what you found and if I've characterized it correctly.

Scott Weiss, MD, Nemours Children's Health (14:14):

Yeah. So the purpose of the PRoMPT BOLUS study was really to answer the question of what is the best crystalloid fluid to use for children who present with septic shock. The reason this is important is because, while saline is the most commonly used crystalloid fluid, it has some downsides. Now, the reason it's the most commonly used is that it's cheap, it's readily accessible, and it's compatible with other medications, which is really important because children with sepsis need a lot of other medications as well. But it has a very high amount of chloride, more than a super physiological amount of chloride compared to human blood. And so giving saline, particularly at high volumes, results in an elevated blood chloride level.

(15:03):

We know from animal studies and from some prior human studies that if you give saline, you end up increasing the blood chloride level, and that's associated with certain harms, including kidney injury. So the PROMPT study was specifically trying to determine if we could prevent hyperchloremia by giving a more balanced fluid with less chloride, would that result in improved patient outcomes?

(15:32):

What we found through that study, which was a massive collaboration of 47 sites across five countries over five years, what we found was that giving balanced fluids rather than saline did indeed reduce the frequency of elevated blood chloride levels, but that did not translate into improved patient-centered outcomes related to the kidney.

(15:58):

And so why is that important? It means that what we're doing right now, the care that we're providing that most emergency medicine providers give to children with fluid, which is mostly saline, is perfectly fine. It's effective, it seems to be safe, and it's a great way to start early resuscitation for children to present with septic shock.

(16:19):

Now, the one thing we don't know and can't fully exclude from this trial is whether there's a subgroup of children who present with the most severe illness who might still benefit from balanced fluid. A study can't answer every single aspect of every question. We have some additional analyses. We will try to tease that out in a little bit more detail, but what people should take from this study is that either saline or balanced fluid are safe and effective, and you should follow whatever your local practice is. And you don't need to worry about changing practice or finding a different fluid. Either fluid is safe and effective and is the right thing to do for children.

Carol Vassar, podcast host/producer (16:58):

This is fabulous work. It's going to be or is published in the New England Journal of Medicine as of April 25th.

Scott Weiss, MD, Nemours Children's Health (17:04):

Yeah. It was released by the journal this morning.

Carol Vassar, podcast host/producer (17:08):

Excellent. What's next? You're going to do more analysis of the PRoMPT BOLUS. What's next for you, Scott?

Scott Weiss, MD, Nemours Children's Health (17:15):

There's still a lot we don't know about why some children with sepsis have poor outcomes, whether that's mortality or morbidity after they leave the hospital. Our prior work has demonstrated that most of the bad outcomes, including death in children with sepsis, occurs over the course of days to a few weeks rather than in the first hours to day in which they present. So that gives us a sense that there's an opportunity to perhaps to intervene if we know the pathophysiology better about why some children either don't recover or continue to get worse from their septic insult. And so the other part of my research program, which Nemours has been very generous to support, is running an NIH-funded lab looking at mitochondrial dysfunction as a mechanism of organ injury in children with sepsis. And so I spent a large part of my time trying to understand whether there's a mitochondrial-based mechanism that is preventing some children from recovering.

(18:29):

And the mitochondria are very important because they ultimately are what allow our cells to provide energy. And it's that lack of energy that seems to drive ongoing organ failure. So if we can understand those mechanisms better, hopefully we can start to identify novel treatments and save those children who currently, even with the best care we know possible right now, we're not able to help.

Carol Vassar, podcast host/producer (18:55):

What gives you hope as we look to improve the outcomes for kids who have sepsis or septic shock?

Scott Weiss, MD, Nemours Children's Health (19:01):

I think there's incredible enthusiasm and support for sepsis as a whole. And that's true at Nemours. The reason we're talking about it now is because it's a priority here, but it's also something that now is increasingly in the public awareness. There's been a lot of momentum in the lay press to better acquaint people with what sepsis is. And that's led to calls for increased research and increased funding so that we can really get to our goal eventually of not having any infant, child, or adult die from sepsis.

Carol Vassar, podcast host/producer (19:51):

Dr. Scott L. Weiss is the Division Chief for Critical Care Medicine and Vice‑Chair for Research in the Department of Pediatrics for Nemours Children’s Health.

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Well Beyond Medicine!

Carol Vassar, podcast host/producer 

Thanks so much to Dr. Weiss for sharing his findings with us, and thank you for listening. 

Dr. Weiss is just one of more than 600 skilled Nemours researchers and research assistants conducting about 300 clinical trials and studies, and publishing in peer-reviewed journals - nearly 600 last year alone - to help create the clinical and scientific foundations of whole child health for generations of kids. Learn more about their research at the link in the show notes for this episode, and join us next time as we talk with Nemours Enterprise Physician-in-Chief & Chief Scientific Officer - research falls squarely in his purview - Dr. Matthew Davis - to hear more about additional research presented at the Pediatric Academic Societies Meeting in Boston, and beyond. Please join us. 

We have nearly 200 episodes of the Nemours Well Beyond Medicine podcast available for you to hear and view. Visit our website, nemourswellbeyond.org to catch up on any episodes you missed. While you’re there, leave us a voicemail with a comment or a podcast episode idea, subscribe to the podcast, and to our monthly enewsletter. That address again is nemourswellbeyond.org. You’ll also find the podcast on your favorite podcast app, the Nemours YouTube Channel, and on your favorite smart speaker. 

Our production team for this episode includes des Susan Masucci, Cheryl Munn, Lauren Teta, and Alex Wall. Video production by SaraKate Reger and Sebastian Reilla. Audio production by me. I’m Carol Vassar. Thanks again for joining us. Until next time, remember, together, we can change children’s health for good - well beyond medicine.