SCCMPod-565 CCM: Key Updates for the 2026 Adult Surviving Sepsis Campaign Guidelines

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Dr. Enfield: Hello, and welcome to the Society of Critical Care Medicine's podcast. I'm your host, Kyle Enfield. Today, I'm speaking with Dr. Massimo Antonelli, MD, and Dr. Hallie C. Prescott, MD, MSc, FCCM, about the Adult Surviving Sepsis Campaign Guidelines. Dr. Massimo Antonelli is a professor of anesthesiology and intensive care medicine at the Catholic University of Rome and Gemelli University Hospital. He is also the chair of that department.

He's also the director of general intensive care unit at the Polizzio A. Gemelli University Hospital. Dr. Hallie Prescott is a professor of pulmonary and critical care medicine at the University of Michigan and a staff physician at the Ann Arbor Veterans Affairs Healthcare System, where her work focuses on improving the care and outcomes of patients with sepsis. I want to welcome you and thank you both for joining us today. And before we start, do either of you have disclosures you want to report?

Dr. Prescott: Yeah, Kyle, thanks so much for having us. I am a consultant for AurobacTherapeutics. That's my only financial conflict of interest to report.

Dr. Antonelli: At present, I do not have any further disclosure about those mentioned into the final manuscript.

Dr. Enfield: I want to start off with the first question about the Surviving Sepsis Campaign Guidelines for 2026. There are about 129 statements, some that are new. For the busy clinician reading the executive summary over coffee this morning, are there two or three headline changes that would reshape how they think about sepsis care this year?

And maybe Hallie, why don't you want to start us off there?

Dr. Prescott: Yeah, sure. Thanks, Kyle. So you're right.

These are large guidelines, quite comprehensive. But in terms of a few things to highlight, I will say that we have a number of new conditional recommendations that are really all focused on trying to speed up diagnosis and treatment. And those include conditional recommendations to screen for sepsis en route to hospital, to administer antibiotics en route to hospital in very select circumstances where the patient has hypotension and prolonged time of transport.

And then we also have a conditional recommendation to use a sepsis huddle, or a code sepsis protocol, which is essentially an implementation strategy to speed up diagnosis and treatment. So those are three key ones.

And then I would say the other kind of big area of emphasis has been thinking about not only timing of antibiotics, but also the antibiotic selection and trying to ensure antimicrobial stewardship at the same time as timely sepsis treatment. So we have new conditional recommendations regarding, for example, when to use anti-anaerobic coverage and a conditional recommendation against use of empiric antifungal therapy outside of very sort of select case-by-case scenarios.

Dr. Enfield: I am sure the IDSA will be excited to hear about antibiotic stewardship and the surviving sepsis guidelines. Massimo, anything else to add?

Dr. Antonelli: At least it's important that during these guidelines, there was great attention to try to be consistent with the antibiotic stewardship in agreement with the recommendations that have been made by the International Infectious Disease Societies.

Dr. Enfield: One of the things that I really enjoyed about these guidelines was that a large number of members came from lower-/middle-income countries. How did that diversity change the conversations and any of the recommendations compared to prior iterations?

Dr. Antonelli: I think it changed substantially. Thirty-eight percent of the panel was represented by panelists working or practicing in lower-/middle-income countries, currently or in the past, 20% currently and 18% previously. Consider also that, despite the fact that most of the panelists came from North America and Europe, there was a diverse representation in Asia, Oceania, South America, Africa, and the Middle East.

What changes? Changes the idea that we should have put great attention on the universal applicability of the guidelines. In other words, even though we know that there are new tools that can be used for the diagnosis, for example, like the rapid diagnostic test, these are not applicable everywhere. But it doesn't mean that the recommendation has no sense. So everything should be graded upon the place where the physicians are.

And another possibility is just looking at those of lactate. You know that the lactate is one of the hallmarks for defining sepsis. But on the other hand, when the lactate levels are not available, you can also use the peripheral refilling time, which is a clinical test, very simple, and adopted everywhere. So the universality of this guideline was one of major points that was reinforced, strengthened by the presence of these 38% of panelists.

Dr. Enfield: That's a great amount of work. And were there any other specific areas where the panelists—the conversation changed because of the inclusion of a more diverse population of intensivists?

Dr. Antonelli: Yes, it was, especially as I mentioned for a while before, the careful antibiotic prescription policy, stressing how important could have been avoiding the administration of antibiotic when this was not necessary, or where there was no confirmation on the laboratory tests, and then avoiding any unnecessary empirical antibiotic approach.

Dr. Enfield: Hallie, you mentioned at the beginning that one of the key changes was in the screening and early recognition, particularly talking about pre-hospital care. Can you speak a little bit more about what that looks like and how that can be implemented both in the U.S. and abroad?

Dr. Prescott: Yeah. So we have a new conditional recommendation to screen for sepsis en route to hospital. We don't provide a specific recommendation about which exact screening tool to use, either in ambulance or in hospital, recognizing that there's a lot of variation in types of tools and the sort of settings where this will be used, and so it needs to be locally adapted.

But in general, I would say the three big buckets that would be included in sepsis screening across the board would be markers of clinical instability or acute organ dysfunction, like altered mental status, signs and symptoms of infection, and then, importantly, risk factors for infection. I think that's particularly important given how common it is to have altered mental status when presenting with sepsis. Not everybody's going to show up telling you this very clear-cut story that they've had signs and symptoms for an infection that have been getting worse over the prior week, so I think it's also important to elicit recent surgery, recent hospital, immunosuppressed status, and trying to put those three things together—clinical instability, signs/symptoms of infection, risk factors for infection—to try to develop your pre-test probability for, gosh, how likely is it that this patient has sepsis, based on the kind of initial presenting vital signs and history before you have any, you know, laboratory tests back.

Dr. Enfield: That's great. And what about pre-hospital antibiotics? Do you make specific recommendations on what ambulances or EMS crews carry with them, or is that left up to local practice and local availability?

Dr. Prescott: Yeah, great question, Kyle. Yeah, I think it's important to talk about this recommendation because it's brand new and also quite narrow, right? So we have a conditional recommendation to screen for sepsis en route, and then we additionally have a conditional recommendation to administer antimicrobial therapy en route to the hospital, but that's a very, very narrow recommendation.

So that's for people with, number one, probable sepsis, meaning after screening, you have high pre-test probability, that's your most likely diagnosis, and they're hypotensive. We know that patients who are hypotensive, that timing is particularly important, and that with delays, mortality goes up. And then finally, that they have a prolonged transport time. So we specifically say over one hour to in-hospital medical evaluation. So certainly there's lots of, you know, urban areas in the world where really this wouldn't be part of the practice because the transport times are short. So I just wanted to highlight that this is, you know, a narrow recommendation for the patients where we know that there are worse outcomes when we delay treatment.

And then in terms of which antibiotics to administer, we do not make a specific recommendation of that. I think that will, you know, sort of depend on local epidemiology. And then we also include a remark that this administration of antibiotics really should only be implemented after an ambulance service has implemented sepsis screening and kind of worked the kinks out for that.

So I would say that would be the sort of first step for implementation is to do a strategy for screening, and then only, after that is in place, to implement antibiotic therapy again in these select scenarios and route to hospital.

Dr. Antonelli: If I may, I would ask that this is a very practical recommendation for the administration of the antibiotic in a pre-hospital phase during transport when we can anticipate time to hospital is over 60 minutes. We know the evidence synthesis suggested that the pre-hospital antibiotic may reduce a 28-day mortality. But on top of that, we have also to consider that we are probably in the Western world, like in Europe or like in United States, not a major issue for the transport of people from the community to the hospital.

But there are other remote regions of Africa, but even Oceania, where very often the transport exceeds the 60 minutes. So having a tool that can just help the paramedics or those who are in the ambulance or the air ambulance to have structured the process for making the diagnosis of sepsis may be very useful for just giving or anticipate the administration of antibiotic on flight or on route.

Dr. Enfield: I recognize that as we've gone through this, you guys have both mentioned conditional recommendations. And for some listeners, that may be a new concept. Could you briefly, before we get too far down the line, kind of tell us what that means?

Dr. Prescott: So our recommendations are either strong recommendations, which are signified with the language of we recommend or conditional recommendations, which are signified with the language of we suggest. And a lot of times like what that means is, you know, like relegated to the methods appendix. But given how crucial it is to understand the implications of these different types of recommendations, new this time, we've actually included a table.

I believe it's Table Two on the implications of strong versus conditional recommendations for different stakeholders, including clinicians, policymakers, researchers. So a conditional recommendation means that this should be done for most patients. It's kind of like the default or the rule of thumb, you know, use it maybe two thirds of the time, but recognizing that there might be important clinical context or sort of resource considerations that would dictate a change from that kind of standard guidance.

These are also recommendations for which additional research may be warranted and which additional research may actually change future recommendations. By contrast, strong recommendations, this is like do for all or most all, you know, 95% of the patients, very few reasons for deviating from that practice and research resources probably better spent addressing other aspects of sepsis management. So yeah, key distinction there.

Dr. Antonelli: If I may add, I think that one important point is that we adopted also a sepsis terminology in the guideline, just categorizing definite sepsis when it is confirmed on clinical examination history and is very unlikely having a different diagnosis. Then probable sepsis, when we have a benign suspicion of sepsis, this remains the most likely diagnosis based on the same things, and it is less likely the probability, the possibility of an alternative diagnosis. When we have possible sepsis, we have a moderate suspicion of sepsis, and sepsis is possible.

However, an alternative diagnosis can be also based upon the similar criteria that can be used for definite and probable. When the sepsis is unlikely, the suspicion of sepsis is very low. And this is important because this terminology has been adopted in many points of the guideline, just in order to be more precise on what we are, what we're meaning when we speak about sepsis.

Dr. Enfield: You all make a distinction in this guideline for recommending NEWS and MEWS over qSOFA. This is really a carryover from the 2021 guideline, but is there a preferred tool, or is this something that's intentionally that's been left flexible in the guideline?

Dr. Prescott: Yeah, I think this is something that has been intentionally left flexible. We have a lot of tools. I would say there's no single best one that is optimal.

There's a lot of variation in terms of how and where these screening tools are used. And so we do allow some local flexibility. So strong recommendation to screen, but we don't have a single tool that we recommend using across the board.

Dr. Enfield: I think along those lines, implementing performance improvement programs in a hospital specifically has really struggled. And you have really tried to suggest the words code sepsis or sepsis huddle in that improvement process. I wonder why those terms, and if you were thinking about the quality improvement leader, what would you suggest to them to make significant changes within their healthcare system?

Dr. Prescott: I think that there's a lot of variability in the language used to describe these, but probably the two terms that are emerging as the most common, at least in North America, are this concept of a sepsis huddle or a code sepsis. And generally, I think these kind of exist along a spectrum and these kind of approaches involve a multidisciplinary team coming to bedside to discuss the patient and expedite the diagnosis and the treatment of a patient determined to have sepsis. So often for a sepsis huddle, it's kind of pulling together the people that are already on the care team for the patient.

So this might be the bedside nurse, the charge nurse, the physician, maybe a pharmacist for that unit or that department of the hospital. And then often when it's a code sepsis, it involves bringing a dedicated response team. So this might be the hospital rapid response team, or some hospitals even have dedicated sepsis response teams, but they all kind of fall under this overarching umbrella of a positive trigger, brings people to bedside, discuss and evaluate the patient, expedite diagnosis and expedite treatment.

Dr. Antonelli: If I may add, this consideration are really worth because the multidisciplinarity of the approach is essential. Please consider that despite this recommendation is so important, nonetheless, there are many situations in many places where this is not adopted at all. And not only in remote regions of the globe, but also in Western countries, like in some areas of the European continent.

So this is something that should be implemented more and more with the principle that the approach taken by specialists of different areas is essential for having strong and effective teamwork.

Dr. Enfield: Yeah, I recognize that we have worked very hard at our code team response for cardiac arrest, and a sepsis response has many of the same important features. One of the things that's really driven the cardiac response approach has also been sort of the push from patient advocates, as well as sort of outcome measures that are being monitored. I wonder, what do we see in the horizon around that with when it comes to sepsis, particularly as we think about the next iteration of these guidelines of how patient advocacy can really fuel hospitals to change practice around sepsis?

Dr. Antonelli: You mean after the discharge or the moment the patients are discharged from the hospital?

Dr. Enfield: No, really, when someone has a cardiac arrest, there is a very protocolized approach that people train for. We specifically have training around that. But when you think about sepsis, we have training, but we don't have sort of the same regimented approach to training that we do when it comes to cardiac arrest.

And I wonder, you know, how do we shape that future state where we think about these along the same spectrum?

Dr. Antonelli: Indeed, there are several aspects that should be considered. For example, you mentioned timing or what concern the antibiotic therapy, antimicrobial therapy administration. We do have a precise situation very well described.

For instance, the discriminant is the shock is present or is absent when the sepsis is definite or probable or in presence or not of shock. In this case, you have to administer the antimicrobial therapy immediately and if possible within one hour of recognition. This is also true when sepsis is possible, but the shock is present.

For what concern the possibility when the sepsis is only possible and the shock is absent. This is the only condition where the rapid assessment of infections may help us and the administration of the therapy can be a bit postponed within three hours if the assessment over this time confirms that the concern for infection persists. So this is an important point.

And something similar, we may also have looking at the hemodynamic, where we have various moments and what we have to do if the patient has sepsis and hypotension and adiabatic lactate, it's distributed between the monitoring that should be careful and immediately you have to measure the lactate or an alternative when the lactate are not possible, the capillary filling time, you need to give fluid within the three hours, the amount that is driven by the famous the mL per kilogram body weight, you need to give it as active agents.

And after all this intervention, if the hypotension persists and the lactate elevation persists, we have to go further and initiate norepinephrine. If it is not already initiated, we have to give additional fluid based on the fluid responsiveness. We have to use balanced solution or we have to assess the fluid responsiveness using dynamic measurements.

And the trend of lactate, the capillary filling time trend can be helpful as well. So there are a sort of decalogue of things that should be taken into consideration in order to treat our patient properly.

Dr. Enfield: I want to turn a little bit to the antibiotic recommendations and the guidelines. The urgency for antibiotics has been maintained. And as you point out, there's an allotment for a little bit slower in the area of possible sepsis without shock.

But there's also the concept of don't delay, but don't over-treat that is brought into these guidelines. And I wonder how you would counsel frontline clinicians to navigate that tension?

Dr. Antonelli: I admit that this is not very easy, but of course, if we can rely upon the essential test that we mentioned up to now and the clinical acumen, when the sepsis is definite or probable, you may feel quite confident in administering the antibiotics. But when there is only the possibility, then you should be very prudent. And what is really important to stress that all these situations should be consistent with the idea of the antibiotic stewardship.

What does it mean? It means that if sepsis occurs in the hospital, you need to know also what is the local epidemiology. You need to know if there are MDR. You need to know if these MDR are very common or were present already in previous infections in our patients. This means that this is not only one aspect that we have to take into consideration, but a congeria of different things that put together, compose a mosaic and drive us to the antibiotic administration in agreement with the antibiotic stewardship policy.

Dr. Enfield: Hallie, I wonder if you might mention a little bit about the antifungal comments within the guidelines.

Dr. Prescott: Oh, yes. Sure.

So kind of as mentioned before, the conditional recommendation is kind of this default practice, rule of thumb. And previously, we had in 2021, two conditional statements regarding antifungal therapy, sort of to avoid it and patients at low risk of fungal infection, but to use empiric fungal therapy in people at high risk. But I think the issue and the reason for the change here is that even in trials that prospectively try to enroll patients at high risk of fungal infection and treat them empirically, we don't find benefit.

And in fact, even high-risk patients in these types of trials, like only a small proportion ultimately end up to have fungal infection. And so that's the reason for the guidance change that kind of like really for most patients, we suggest against empiric antifungal therapy. And now we have just a remark saying that empiric antifungal therapy can be used in a case-by-case basis in selected patients with septic or septic shock based on risk factors, including immunosuppression, prolonged use of antibiotics, prolonged hospitalization, intra-abdominal sores.

So I think I can share, you know, this is outside of the guideline or whatever, but I can share kind of my own personal practice, is that when patients come in, generally, I'll start them on empiric therapy covering bacterial causes of infection that's really guided by their site of infection. And to be honest, if we initiate patients on antibacterial therapy and work on hemodynamic resuscitation, within the next few hours, you'd hope to see that the patient is showing some signs of improvement, meaning that, you know, vasopressor doses coming down or vasopressor dose was rising, but now has plateaued. If you see a patient that you come in, you initiate them on empiric coverage for the suspected sites of infection, and they just continue to get sicker despite everything that you're doing.

That's when we want to kind of ask this question of, like, gosh, what might we have missed? Should we add, at this point, antifungal therapy? And also, you know, making sure that no source control issue was missed.

So that's how I've sort of implemented this into my practice. Is it something that I sort of quick reassess some of the patients at sort of hour three to four to say like, are we moving the trajectory? Is our treatments helping this patient? If the answer is no, and this patient is getting continuously sicker, then this would be the case-by-case scenario, again, guided by risk factors where you might initiate antifungal therapy, but not across the board for patients, you know, as they come into the ICU.

Dr. Enfield: And this is really one of those areas where new research guided and changed the guidelines recommendation, it sounds like.

Dr. Prescott: Yeah, I think the fact that, you know, there really haven't successfully to date been trials that have been able to isolate a prospective population of patients that benefits has converted us to having a conditional recommendation against this across the board. But again, this remark kind of allowing clinical acumen, you know, allowing to respond to what's, you know, being seen at bedside. Yeah.

Dr. Enfield: You guys have both brought up a couple of comments about the hemodynamic resuscitation. One of the things that I noted in the guidelines was that with the 30 mLs per kilogram crystalloid recommendation, there's some language about adjustment for body weight over a BMI of 30 and frequent reassessment. I wonder if you could talk a little bit, Massimo, about where this language came from and what was the conversation within the committee when they were thinking about it?

Dr. Antonelli: There was a very careful conversation concerning that. And one of the first thing is that despite that the 30 mL per kilogram body weight for intravenous fluid is recommended, it should be always taken into consideration the individual patient characteristics and the context. I can give you an example.

If you have to prescribe fluid, you need to be very sure that you avoid any harm for under or over resuscitation in your patient. If your patient does have a cardiac failure, for example, it is more than obvious that you can give such a huge amount of fluid, then you should use fluid challenges, for example. Then the individual characteristics are fundamental.

The weight-based fluid volume, in general, is calculated on the actual body weight or can be adjusted. Or ideal body weight, especially when we take into consideration people who are overweight, obese, and when their body mass index exceeds 30 kilograms per meter. So we have the principle.

We have to give the 30 mL per kilogram body fluid, but we cannot keep from the consideration of the context.

Dr. Enfield: And I wonder if in these guidelines, how the CLOVERS trial and really sort of the cultural shift to more restrictive fluids influenced how the committee approached the recommendations.

Dr. Antonelli: For sure, the influence of these trials was important for expanded discussion between the panelists. And the final proposal is then of being careful and that amount of fluid should be given anyway, or should try to give anyway, depending on the condition. But if you adopt a more restrictive strategy, you can be sure that it doesn't cause any harm to the patient.

Dr. Prescott: Yeah. I think with CLASSIC and CLOVERS both coming out and being negative trials, I shouldn't say negative, but really sort of not favoring one arm or the other, I think it sort of led to this evolution of that, well, probably we should not be doing just a generally fluid heavy versus a generally fluid light approach to resuscitation. But we have also conditional recommendation for ongoing resuscitation being guided by dynamic assessment of fluid resuscitation.

And so probably after this kind of initial pragmatic bolus transitioning to a more personalized approach is the way to go. And the strength of evidence was upgraded slightly for this recommendation for this more tailored approach based on dynamic reassessment. And I guess the other thing I'll just mention is in CLASSIC and CLOVERS is that, yeah, those were largely studies of ongoing approach to resuscitation. So they didn't weigh in so much about this question about the initial 30 mL per kg fluid bolus, because most patients had gotten around that much by the time they were in the trial or shortly after enrollment.

Dr. Enfield: I also noted that the guidelines now do favor balanced crystalloids over normal saline. If you had to guess, does this mean that the debate over saline versus balanced fluids is over, or are we going to still see ongoing trials and arguments about these different approaches?

Dr. Antonelli: For the moment, there are still trials ongoing. Still, for instance, we have the ALBIOSS II trial that should be published, I hope very soon, and where when you have to give a balanced solution in a large amount, you may take or not into consideration the use of albumin. Think about the fact that in the previous iteration in 2021, this was recommended when there was an excessive amount of fluid should be given.

Now, in the present recommendation, there is a downgrade of that, and the use of albumin is suggested only when there is specific situation, like the excessive overload of fluid, and would be over in presence of, say, cirrhosis, but should be absolutely suspended and avoided when a patient has a brain injury or a vascular injury in the brain. So, I think that there will be, for the future, room for expanded research in the field, and we are waiting for future new assessments.

Dr. Prescott: I can chime in and talk a little bit about the type of crystalloid. I think you mentioned, Kyle, that we have a conditional recommendation to use balanced crystalloids such as lactated ringers over saline. Really, for most all patients with sepsis, there is one remark that saline is still preferred specifically for patients with traumatic brain injury, and so that would kind of trump sepsis, but otherwise, outside of a trauma, balanced crystalloids should be the default fluid, and this was upgraded in terms of the certainty of evidence rating, so it went from low certainty to moderate certainty evidence, and we did have some discussion about whether this should be a strong recommendation given the upgraded certainty of evidence, but there are still some ongoing trials addressing this question, and then if we sort of go back to the implications of strong versus conditional recommendations, a strong recommendation says research resources are better spent otherwhere, so it's sort of saying the guidelines come down and say, like, we don't really think that there should be ongoing trials on this topic, and we didn't necessarily felt it rose to that level, so I think that ongoing trials are okay, you know, that will sort of further provide evidence to the field, but really, outside of trials, I think that the evidence, again, is stronger than it was last round and really suggests that in routine practice, outside of clinical trials, balanced solution should be the sort of default fluid of choice in patients with sepsis.

Dr. Enfield: I was also excited to see, and you touched on this just a minute ago about the more patient-specific approach, particularly in thinking about cardiac dysfunction more specifically, and bringing in epinephrine and norepinephrine as a first line. I wonder if you could walk us through the updated vasopressor algorithm. Massimo, maybe you start with you, and then Hallie, if you have some add-ons there, that would be great.

Dr. Antonelli: For sure, the norepinephrine remains the first line vasopressors, and you know that if you look at the recommendations in comparison to what we had in the previous guidelines, we have a different grading, and we have a stronger recommendation concerning epinephrine, but a conditional recommendation with a low certainty of evidence, with a very low certainty of evidence when the other or the second agent should be vasopressin or angiotensin. And then I think that still it represents the first line intervention.

But I guess that it's important to consider that when the cardiac failure is present, one thing that can be used is once again the butamine, and it is suggested also to use when this is not available in certain areas of the world, the epinephrine as an agent for the cardiac dysfunction compensation.

Dr. Enfield: And any thoughts, Hallie, about where angiotensin today really falls in these guidelines?

Dr. Prescott: Yeah, great question. So angiotensin still has limited data behind it. I think there's theoretical reasons why it may be beneficial to have a more multimodal vasopressor approach as opposed to adding on more catecholamines.

But generally, angiotensin is more expensive, less widely available around the globe. And so when you go down our evidence-to-decision framework, which we use and think about these critical factors about availability and costs and things like that, we are not able to include conditional recommendations of angiotensin above these other more widely available and less expensive vasopressor therapies. But certainly, I think, is an area that warrants future research.

I think beyond kind of first and maybe second line vasopressors, we have very sort of low or very low certainty evidence guiding a lot of the sort of ongoing approaches to resuscitation.

Dr. Enfield: These guidelines, for the first time, included methylene blue and beta blockers. I wonder if you, Massimo, might talk about what the panel has concluded and what research gaps in these areas that need to be studied further.

Dr. Antonelli: Well, the methylene blue was indeed not sufficiently recommendable and there was no real evidence coming from the scientific literature and from the meta-analysis that this can be a real solution for the patient. However, we have to consider that having the insufficient evidence, we just promulgate a few remarks. While methylene blue may improve the pressure, the evidence insufficient to determine can be used as a rescue therapy, improving the survival.

For sure, apparently, some patients with potential treatable disease may value a trial and then the possibility of attempting this approach. However, being present these discrepancies within the panel, we launched a sort of internal survey and in our practice, in the end, we could establish that 69% of the panelists never or almost never use methylene blue as a rescue therapy, 23% sometimes use it, 6% usually use it, and 1.1% almost always use it. So, you may see how different may be the approach. Prevalently, it is never used, almost never used, or whether.

Dr. Prescott: Oh, methylene blue was just a challenging one. We actually did have, you know, a fair amount of discussion on this question. And I would say one of the things that, you know, is always a challenge when making guidelines is trying to suss out, right, like at what level of evidence do you generate a recommendation, you know, versus continue to say insufficient evidence.

And so, we included a new figure in the guidelines. This is Figure One that talks about sort of how we went through this process of developing statements. And I would say we provided some fine print here, but factors that we considered when deciding to issue a graded recommendation on very low certainty evidence versus not include these other aspects of the decision framework.

So, equity, feasibility, acceptability, whether we'd previously in prior guidelines issued a statement whether the intervention is available and whether the intervention is already in routine use. And so, certainly, I think methylene blue is, at least in many parts of the world, is not in routine use. You know, we haven't had a statement before.

And so, you know, that leads us to be a little bit more conservative about issuing a statement. But it's interesting with that panel survey, you know, that there are certain parts of the world that I think this is more common. And I think the reason is that there are certain second and third line vasopressors that are just not widely available around the world, right?

So, it may be like you have epinephrine or norepinephrine and then, you know, the only other thing you have to escalate to is methylene blue. And so, the remark, you know, like acknowledges that patients may definitely warrant a trial. And then I think in other parts of the world where there's greater availability of vasopressors, there's dramatically less use in practice.

So, this is where, you know, I think it was very helpful having this global panel and, you know, being able to do these panel surveys and sort of understanding the heterogeneity and the sort of resource availability and the context by which people practice.

Dr. Antonelli: There was also a discussion concerning the other joint additional therapies. And in the end, we suggested against the use of the antipyretic drug, vitamin C, immunoglobulins, blood purification, polymyxin B, hemoperfusion, vitamin D, exubergine, and probiotics. Even though the antipyretic therapy, even though it had a very uncertain effect on mortality, can be done for the symptom control.

Vitamin C has six trials, now 55 randomized controlled trials. Many trials were small, single center, and high risk of bias. And there was no difference in 90-day mortality in seven of these randomized trials and with low risk of bias.

So, in the end, these adjunctive therapies were not very used. Maybe one that can be useful to mention, but we couldn't include into the guidelines, is the recently TIGRIS studies for the polymyxin B hemoperfusion. And the authors has enrolled patients with a endotoxin level between 0.6 and 0.89, and who had a condition of septic shock where fluid resuscitated. And in the end, there was an approach through the Bayesian analysis that was in favor of improvement in mortality. But this should be, for the moment, looked with a lot of prudence. And the opportunity to include these in the next guidelines may be an option to be discussed for the future.

Dr. Enfield: One of the things that I've noticed more and more about guidelines that are coming out is looking to survivorship, but also elements of family communication. I know that there are some comments within the guidelines regarding signposting as well as trials of critical care. Howie, could you talk a little bit to the clinician in the room who is struggling with helping families understand outcomes and probable outcomes, and how signposting and trials of critical care can really facilitate those discussions?

Dr. Prescott: Yeah, right. So that's a new question we addressed was time-limited trials. And we ultimately issued a statement of no recommendation.

And I think there's ongoing research in this space. But I do think it can be a helpful thing to use on a case-by-case basis. So essentially, this is explicitly discussing uncertainty and talking about using critical care in a time-limited fashion, and then basing ongoing care based on response to this initial trial.

And I think this is super helpful because, at least in the US, there's a lot of people who have advanced directives that say something like, I don't want to be kept on life support forever. However, I want life support for a short period of time in the event of critical illness. And so then family members are really left, I think, shouldering a lot and feeling like they are the ones making the decision, even though ultimately the critical illness drives outcome.

But I think it leaves a sense of responsibility or this moral distress that they are deciding what happens to the patients. And so a time-limited trial is nice because you can say, we're uncertain. Even with our best tools, suppose someone has a 90% probability of mortality, that still means a 1 in 10 chance they survive.

And a lot of people would want to take that chance, right? So in a time-limited trial, there's an explicit discussion of uncertainty, a decision to go forth and use full support of life support, but a decision to reassess what that gets us within 48 to 72 hours, and often a decision to say, if the patient is making progress and looks to be showing signs of recovery, we'll continue to support. But if 48 to 72 hours from now, the patient continues to be sicker, they're sort of deteriorating or failing to show signs of improvement, then we'll shift our goals to palliation, providing high-quality, end-of-life care.

And so, I mean, this is definitely something that I use in my practice and I feel helps provide structure and sort of a sense of control in what can be like a really murky, challenging decisional scenario where I think there's a lot of distress borne out by loved ones.

Dr. Antonelli: I would like just to stress how important has been the support given by patient-family associations that contributed a lot, giving the perspective and at least reorienting some of the suggestions and recommendations in a way that could take in great importance the opinion of patients and families that, at times, may be different to the perception that a physician may have.

Dr. Enfield: Yeah, I think that recognizing the desires of families and taking that into account in our discussions is so crucial. And I think along those lines is also talking to families about survivorship. I know that many of these are carryover conversations from 2021, but we still have a lack of evidence on specifically cognitive outcomes following sepsis, but we know that there is impairment.

What should clinicians be doing to counsel families early in the course of sepsis and as their care goes on in the hospital?

Dr. Antonelli: The real matter is that we do not have enough evidence to make any recommendation regarding the cognition-targeted therapies versus usual care. And the other important thing is that in our opinion, at the end of the discussions, when you have the cognitive-targeted therapies being used or available, it is very reasonable to use them. And in general, very accepted and feasible, let's say.

However, we cannot deny that this should be considered a priority for the future, also for evaluating the cost-effectiveness of these cognition therapies after sepsis and septic shock. And this information is completely lacking at the moment.

Dr. Prescott: Yeah, I think it's very common, right, that patients after sepsis experience kind of cloudy or foggy thinking. And then, you know, for some patients, it's much more extreme, right? Like true sort of ongoing sort of cognitive impairment or sort of dementia states.

And then also like sort of functional limitation, decreased strength, decreased stamina. And time and time again, you'll hear from patients, right, who leave the hospital and they, you know, really sort of go on to struggle, right? They have difficulty sort of concentrating, difficulty doing the tasks they used to do.

One of the things that sort of commonly hear is that they feel like it's sort of like a personal failure on their part. They feel that, you know, like this were so common, like clearly somebody would have told me about it. And so I think that's one of the reasons why it's so important to counsel patients to expect this, that they're not alone, right?

That this is something that's experienced commonly. And, you know, often we do see recovery. And then when people have decreased strength and stamina, it is important to try to start with what you can do, but sort of gradually increase your activity kind of day by day during recovery.

And then not this time, but the prior time for the 2021 guidelines, I chaired the patient panel. And I remember having this long discussion about best practices for educating patients and the things that came through from the patient panel are number one, sort of multimodal, right? Like if you can have conversations, but also provide pamphlets or flyers, or even educational videos, having this material in different formats is helpful.

And then the second thing that came through loud and clear was like, this isn't just like a one-time counseling session, but really an ongoing conversation. One of the patients said, I kind of get the sense doctors have a checkbox, like tell patient about long-term outcomes, check, done. And they were saying just, you know, that it's very overwhelming, you know, there's so much going on and that this is something that sort of just, you know, needs to be part of the conversation, you know, as people are preparing for discharge and as they're being seen in the outpatient setting.

And that just really felt like, you know, like good pragmatic advice, and of course made good sense. And I'm probably like guilty as charged. I think all internists walk around with a paper, with a bunch of checkboxes of the things we need to get done.

And so thinking beyond that, about having this be an ongoing conversation, I think is really important.

Dr. Enfield: I think the checkboxes are a carryover from when we were interns specifically. So I think it's something we can't get around. I guess my follow-up question to that, as someone who has a post-ICU discharge clinic that often has more patients scheduled than show up for, I worry that these guidelines are going to be seen by intensivists, maybe some internist hospitalists that work on sepsis committees in their hospital and fall deaf on the primary care doctor who is seeing this patient in the outpatient arena.

And how do we as a society, and I realize this is not what the guidelines covered, but how does SCCM and others reach to our primary care physicians and educate them on this need to continue the conversation following discharge about what to expect from sepsis?

Dr. Prescott: Yeah. I think it needs to start kind of from the very beginning, like in medical school. This, I mean, I had a sort of limited sort of formal classroom instruction on sepsis, and I'm pretty sure absolutely none about sort of post-sepsis syndrome or these kind of longer-term aftereffects.

So I think it's something that we just need to educate people on from the very beginning as they go through medical school. And then I also think that there are a number of excellent organizations that are sort of trying to bridge this gap and provide resources both to patients and also families and primary care physicians. So like specifically Sepsis Alliance, which has kind of online communities for peer-to-peer support for patients and families impacted by sepsis, and also just has an amazing sepsis institute of educational materials for sepsis coordinators, but really, really everybody who is sort of part of the big sort of team sport taking care of patients before, during, and after sepsis.

Dr. Antonelli: The real essence is just to give continuity to the care that we deliver in the hospital also after the discharge, which means the close contact between the family doctor and the doctors who do care about the septic patients in the hospital. Transmitting all the therapies and the medical report in order that this could be known into detail by the family doctors.

Dr. Enfield: Yeah, I think that's an excellent place for us to start wrapping up. I wonder, Massimo, is there anything that you wish we had talked about in this conversation that you really want to emphasize for the clinician who is listening to this and trying to tackle all these guidelines?

Dr. Antonelli: Yes. As a recommendation in general, please don't stop your reading to the recommendation and at least the remark, but go deeper into better insights, reading the rationale that often explains the real reason or a conditional or strong recommendation. Personally, if I can, I would like just to emphasize a little bit something that we haven't spoken about that introduced the concept of de-resuscitation and pertains a conditional recommendation with very low certainty of evidence where we recommend the active fluid removal after the resuscitation phase.

We have noticed that, indeed, very often in order to make the patient survive, we deliver a large amount of fluids. We have already mentioned that. And together with the ongoing doses of vasopressors, at the very end, the need of ongoing expansion generates also an accumulation of fluid. In the end of the resuscitation phase, the active fluid removal in general through diuretics is fundamental. And if it is insufficient, the remark suggests also to use ultrafiltration or at least extracorporeal fluid removal.

Dr. Enfield: Thank you so much for bringing that up. That was, I think, an important statement in this 2026 guidelines. Hallie, anything from your perspective that we missed today to talk about?

Dr. Prescott: Yeah, I'll underscore Massimo's suggestion to read the narratives. I think there were two things that we tried to do systematically throughout the guidelines. The first is to make comments in the narrative about how this recommendation should be adapted to low resource settings.

So that's something we did systematically. And then the second was how this relates to other guidelines. So we know how frustrating it is when guidance seemingly differs between guideline A versus guideline B.

So we tried to always provide commentary about, well, gosh, this is pretty much identical to what's recommended in these or those other guidelines. And then in areas where there's differences or the phrasing is such that it could be perceived as a difference, we explain the rationale kind of for why we ended up with this recommendation as opposed to what was stated in other guidelines. And so the hope is to try to have greater clarity and sort of demystify the process for going from evidence to guidelines.

Dr. Enfield: Well, thank you both and thank your committee. I know that guideline creation is a Herculean task to say the least and often goes unnoticed, but it's so valuable to our community. This will conclude another episode of the Society of Critical Care Medicine's podcast.

I encourage every listener to download the new guidelines for 2026 for surviving sepsis and read them and think about how they can implement these guidelines within their local practice. If you enjoyed listening to this podcast, please rate and leave a review. For the Society of Critical Care Medicine podcast, I'm Kyle Enfield.

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Kyle B. Enfield, MD, is an Associate Professor of Medicine in the Division of Pulmonary and Critical Care at the University of Virginia.

He received his undergraduate degree from the University of Oklahoma. Join or renew your membership with SCCM, the only multi-professional society dedicated exclusively to the advancement of critical care. Contact a Customer Service Representative at 847-827-6888 or visit sccm.org/membership for more information. The SCCM Podcast is the copyrighted material of the Society of Critical Care Medicine, and all rights are reserved. Find more episodes at sccm.org/podcast. This podcast is for educational purposes only.

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