Become a Creator today!Start creating today - Share your story with the world!
Start for free
00:00:00
00:00:01
Surviving sepsis campaign 2026 guidelines
1.2k Plays12 days ago
In this episode, Dr. Zanotti discusses the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. He is joined by Dr. Hallie Prescot and Dr. Bram Rochwerg. Dr. Hallie Prescott is an Associate Professor in Pulmonary & Critical Care Medicine at the University of Michigan and a staff physician at the Ann Arbor Veterans Affairs Healthcare System. She serves as co-chair of the international Surviving Sepsis Campaign Guidelines. Dr. Bram Rochwerg is an associate professor and critical care physician at McMaster University in Hamilton, Ontario, Canada. He is co-vice-chair of the Surviving Sepsis Campaign Adult Guidelines.
Additional Resources:
SCCM Point-of-Care (POC) APP:
https://play.google.com/store/apps/details?id=org.sccm.mobl&hl=en
https://apps.apple.com/us/app/sccm-poc/id1079591546
Books and music mentioned in this episode:
William Osler: A Life in Medicine. By Michael Bliss
Blood Poison: The Untold Story of Sepsis. By Parsa Shahinpoor
Recommended
Transcript
Introduction and Overview
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine. Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com. And now your host, Dr. Sergio Zanotti.
Understanding Sepsis
00:00:33
Speaker
Sepsis, defined life-threatening acute organ dysfunction due to infection, is a leading cause of morbidity and mortality in the world. Early identification and time-sensitive critical care interventions are essential to improve patient outcomes.
Exploring Sepsis Guidelines
00:00:46
Speaker
In today's episode of Critical Matters, we will discuss the Surviving Sepsis Campaign, International Guidelines for Management of Sepsis and Septic Shock 2026.
00:00:56
Speaker
These guidelines are comprehensive, and today we will focus on key recommendations centered around methodology, early management, infection, hemodynamic management, it and supportive therapies. For further details, we encourage our listeners to access the full guidelines and the executive summary for the guidelines, both of which are open access publications and linked on our show notes.
00:01:17
Speaker
Our guests today are Dr. Hallie Prescott and Dr. Bram Rockwork. Dr. Hallie Prescott is an associate professor in pulmonary and critical care medicine at the University of Michigan and a staff physician at the Ann Arbor Veterans Affairs Healthcare care System. She serves as co-chair of the International Surviving Sepsis Campaign Guidelines and as lead for the Michigan Hospital Medicine Safety Consortium's Sepsis Initiative.
00:01:39
Speaker
Dr. Ram Rockberg is an associate professor and critical care physician at McMaster University in Hamilton, Ontario, Canada. He's an associate editor at Critical Care Medicine and is co-vice chair of the Surviving Sepsis Campaign Adult Guidelines.
00:01:53
Speaker
Both are recognized clinicians, educators, and researchers with an interest in sepsis and septic shock. It a true honor and privilege to have them today as our expert guest to discuss sepsis.
00:02:03
Speaker
Hallie and Ram, welcome to Critical Matters. Thanks so much for having us. Yeah, it's great. Thanks for the invitation, Sergio. I would love to to start with ah an overview of the guideline
Developing Sepsis Guidelines
00:02:15
Speaker
development. Maybe, Hallie, you can tell us about the committee composition, sponsorship of these guidelines, and the endorsing professional societies involved.
00:02:25
Speaker
Yeah, sounds great. So the Surviving Sepsis Campaign Guideline Panel had 69 members. um This was a truly diverse panel. There was representation from 23 countries and 38 percent of the panel either currently or previously practice in a low or middle income country.
00:02:44
Speaker
um And the sort of most common regions of the rural world that people come from are North America or Europe, um but 35 percent of the panel comes from outside of those regions. So I think that was just super important because, you know, there's huge you know variation in terms of like resources and perspectives. And so, you know, we had a good diversity of representation, which led to you know really rich discussions.
00:03:07
Speaker
um So in terms of those 69 members, 25 of them were appointed directly through um professional societies that were invited to sponsor and appoint a representative. And then the others were appointed through the European Society of Intensive Care Medicine or the U.S. Society of Critical Care Medicine to really kind of like round out um you know expertise in the different clinical areas. um So once um you know individuals are appointed to the panel, they then get assigned to a working group.
Formulating and Assessing Recommendations
00:03:41
Speaker
um We had six different subgroups in the guideline and those were screening and early management, infection, hemodynamics, respiratory support, additional or adjunctive therapies for sepsis, and then a group that addressed goals of care, transitions of care and long-term outcomes.
00:04:01
Speaker
Additionally, we had a patient and family panel. This was actually co-chaired by Bram and our other vice chair, Lenny. And this was great. They were you know really involved throughout the process, weighed in with you know their values, preferences, also helped us to prioritize outcomes.
00:04:20
Speaker
um So, within each of those six different working groups, the first step of the guidelines was to define and prioritize clinical questions to be addressed in the guideline. And those are all formed in this PICO format, meaning we define the population of interest, the intervention, the comparator, and then we prioritize the outcomes of interest, typically focusing on about seven patient-important outcomes.
00:04:46
Speaker
We then do systematic reviews for each of the questions, and those are led by a research librarian in close collaboration with a methodology expert. There was one on each subgroup, as well as the clinical experts.
00:04:59
Speaker
Once that was completed, we then did evidence synthesis. where We extract data from the identified studies, do meta-analysis, um and analysis.
00:05:10
Speaker
pre-specified subgroup analyses, as well as assessing risk of bias. And then we assess the certainty of evidence and complete standardized evidence profiles, all according to grade methodology. And in terms of assessing certainty of evidence, you know, that really focuses initially on the type of evidence, whether it's randomized trials versus non-randomized study. But then there's different factors that can either upgrade or downgrade. And ultimately, you're left with a certainty of evidence spanning from very low to high.
00:05:41
Speaker
After that's been done, we would then meet together in our subgroup to review those evidence synthesis and then use this structured process called the evidence to decision framework, essentially a worksheet that we complete where we go through a number of aspects before developing a draft recommendation. So we review the certainty of evidence.
00:06:00
Speaker
the balance of undesirable and desirable effects, the values and preferences related to those effects, the resource use, as well as implications for equity, equity acceptability and feasibility. So really only after having this really sort of comprehensive sort of run through of all the evidence and the sort of you know contextualizing that, Dewey then developed a draft recommendation And anytime there's at least low certainty evidence, we formulated a graded recommendation that ranges from a strong recommendation, you know, we recommend to a conditional recommendation, we suggest over to a conditional recommendation against or a strong recommendation against.
00:06:42
Speaker
And then in the instance of having only very low certainty evidence, those were really handled more on a case-by-case basis. So sometimes we made graded recommendations on very low certainty evidence, and other times we issue statements of no recommendation. And so there's a number of factors that go into that. That includes, you know, different aspects of that evidence-to-decision framework, things like impacts on resource use, equity, feasibility, acceptability, you know whether we'd made a graded statement previously on this particular intervention, whether the intervention is widely available, and you know whether it's already in routine use. So there's a lot of different things that kind of play into that. And we have a a figure in the guidelines, it's figure one, I believe, that shows this kind of decision framework and how we you know walk through it and decide whether to issue a graded statement versus a statement of no recommendation, and then the sort of very select circumstances under which we issue what's called a good practice statement, which is, um you know, something like clinicians should or health systems should do this.
00:07:47
Speaker
um It's also important to recognize that, you know, the implications of these types of statements are different. So these strong we recommend versus conditional we suggest.
00:07:58
Speaker
And we've also included a table, table two in the guidelines to talk about the different implications. So for strong recommendation, this is really something that we should do for all or most all patients. There's really sort of less need for shared decision making or contextualization. um These are more appropriate for policy or performance measure. and also things for which probably research dollars are better spent elsewhere.
00:08:24
Speaker
By contrast, conditional recommendations, which are more common in the guidelines, those are really like the default practice, the rule of thumb. Most patients should get this, many would want this, but there's also reasons why, you know, context matters and, you know, you should consider shared decision making.
00:08:42
Speaker
These ones are less appropriate for policy or performance measure and also areas where importantly, research is still warranted and may change future guidance. So really important to understand the difference between strong versus conditional recommendations.
Finalizing Guidelines with Expert Consensus
00:08:56
Speaker
All right. So after we have those draft recommendations, um we all were very fortunate. We came together in person in March of 2025 and had two days of in-person discussion about the draft recommendations. That was critical. You know, make sure that, you know, We hadn't missed anything. Also make sure that the language being used was clear and concise. And then the subgroups were able to take that feedback um back, um sort of meet again and make sort of final tweaks to their statements before we commenced with voting.
00:09:29
Speaker
And so for a statement to show up in the guidelines, we require that at least 75% of panelists vote and that among those people voting that there's over 80% agreement. And you know in true reality, we end up having greater than 98%, essentially all people voting on nearly every single record recommendation that they were eligible to vote on. And then for all but just a small handful of statements in the guideline, we had over 90% consensus.
00:09:59
Speaker
So that's kind of the process in a nutshell. You know, there's a lot of work and really a lot of rigor that goes into it and following essentially the standards of trustworthy clinical practice guidelines.
00:10:11
Speaker
Excellent. And as you were mentioning before we recorded, there are, I think, 129 recommendations. So obviously, a lot of people involved, a lot of work and Both of you as a co-chair and co-vice chair, I think, are speaking on behalf of the group. But through you, I want to thank the whole committee for all their work, for something so important. You talked about greater recommendations and the implication that these have in terms of practice. You also mentioned good practice statements. I also saw that there are a group of in-art practice statements. Could you comment on that, Hailey?
Clarifying Sepsis Diagnosis and Management
00:10:45
Speaker
Yeah, yeah. Thanks for bringing that up. So this was something that we brought in you know, more formally and systematically this time. So um there's a lot of scenarios where we have only very low certainty of evidence and even some places where we had you know really no evidence at at all and had to issue a statement of no recommendation. And we know how frustrating that is to the field, right? You like read a guideline and says, oh, you know, we have no recommendation about this. So um we essentially asked the question of would it be helpful to the field to have additional information on the panel's practice and wherever we thought that would be helpful we did a survey of the panel just to say you know in your routine practice you know do you do this or how commonly do you do this and we report those out so those are um always start with the statement of in our practice And so they're clearly presented as, you know, not being formal advice or guidance.
00:11:39
Speaker
um But certainly for for scenarios that are, you know, there's a lot of sort of, you know, context variability and limited evidence. I do think that that is probably helpful information. So I think there's 13 different um interventions for which we provide these in our practice statements and just report what the panel is currently doing and with that intervention.
00:11:59
Speaker
And these ah obviously highlight also the uncertainty we have in clinical practice. We don't have answers for everything, but I do i did find them actually instructive as I was reading because it gives you a little bit more context and information of where people are practicing and what still needs to be studied it and perhaps requires more data to make formal recommendations.
00:12:20
Speaker
The other aspect I wanted to ask before we dive into the recommendations themselves relates to terminology. And obviously, and calling things by the right name is always important when we talk about a syndrome such as sepsis.
00:12:36
Speaker
So you've defined for the the purpose of these guidelines, sepsis through the SEP3 definition. But there's also additional terminology that is important for understanding these recommendations. Could you comment on these?
00:12:51
Speaker
Yeah, yeah, absolutely. So we have used these terms of definite, probable, possible and unlikely sepsis. And really, those are meant to have clarity of language when you're sort of talking about this common scenario in clinical practice where, you know, the patient shows up.
00:13:08
Speaker
And initially, you know, before you've even talked to this patient, you you really don't know what they're presenting with. And then, you know, over time, as you gain more information through your history and your exam and sort of the initial initial diagnostic evaluation, you have this kind of like evolving clarity in terms of what the diagnosis is. And so when you think about, you know, like the sepsis three definition, it's really not getting at that. Really, it's really trying to say, you know, what is the definition of sepsis? And so we use these terms to sort of clarify kind of where we are in the process of diagnosing a patient. So definite sepsis means essentially sepsis is confirmed.
00:13:42
Speaker
Probable sepsis means you have a very high suspicion for sepsis. And this is actually the most likely diagnosis for this patient based on what you know from history, clinical examination and the diagnostic testing. And that alternative diagnosis is felt to be less likely.
00:13:57
Speaker
And then possible sepsis, this is a moderate suspicion. This means sepsis is one of the possible diagnosis being considered, but that an alternative diagnosis is also likely based on history, exam and diagnostic testing. So we wanted to be sort of precise about what those meant. So we spent a fair amount of time actually kind of like workshopping those definitions, again, really trying to be clear, particularly very early on when we're talking about recommendations related to screening for sepsis, you know, sort of, you know, when to initiate antibiotic therapy for patients.
00:14:32
Speaker
Excellent. Bram, I would like to get some comments on the screening and early management recommendations. There are several, but I would like to start with ah performance improvement programs, which, by the way, is something that Ellie has talked to on the podcast before, and will'll link we'll link this in the in the show notes. Okay.
00:14:53
Speaker
Yeah, thanks, Sergio. And wow, every time I listen to Hallie go over the process, you know, always impressed by the rigor that that goes into these guidelines. there's There's no doubt that it benefited from the group of experts and and as comprehensive approaches we took.
00:15:06
Speaker
You know, each of us, ah in addition to serving on leadership, also participated with one of the individual subgroups. I'll be honest, Hemodynamics was my subgroup, which we might talk about soon, I think. and it was not screening and early management. But as Hallie said, we were there for discussions that were ongoing in our in-person meeting in Chicago and aware of some of the intricacies of these recommendations. And and I think this is really you know the epitome of of the guideline is that using performance improvement programs to try and get better at things like screening and operating procedures, improving quality improvement strategies, this is this is how we do better for the future, right? and Some of these, you you know, you can see that the evidence for some of these is is less robust. Although when you come to quality improvement strategies and screening, there is is fairly good data to show that this improves, you know, at a hospital level and a systems level, our management of patients with sepsis and also improves outcomes. So I think this was fundamental. It was good thing. building on the recommendations that were made in 2021 in terms of ensuring that performance improvement programs were part of any hospital-based approach. And, you know, it does recognize that there's going to be some variability depending on the hospital and the system around how this is operationalized, what's practical, how it's how it's monitored, but but it's important to undertake.
00:16:23
Speaker
and And when we look at the history of the guidelines over 20 plus years, from my perspective as a clinician, what's been ah a true lesson is that it's not so much that what we do changes over time, but having a standardized approach, evidence-based approach does improve the care of these patients. And we should keep pushing forward. And I think this is very important for our our listeners to push this forward if you don't have it in your hospital system.
00:16:51
Speaker
Absolutely agree, right? You're 129 recommendations, Sergio. You're always going to find recommendations that you agree with, ones that don't, ones that are consistent with your practice. And, you know, it's important to chat through those details, but to know that, you know, again, as you say, a robust process, methodologically rigorous, and we know that that use of these guidelines, translation of these guidelines and into bedside practice has improved outcomes of sepsis patients over time, and we have data to back that up. So I think it's it's really important to make sure that that QI piece of things is not lost.
00:17:22
Speaker
I would like to ask you about diagnosis of sepsis.
Diagnosis Techniques: Blood Cultures vs Biomarkers
00:17:25
Speaker
i'm I'm old enough that I was actually in training when there was a paradigm shift in sepsis and people started talking about it as a emergency, as a time sensitive disease that actually had a higher mortality than many other diseases that we were treating in the ICU, such as acute MI that were treated with that time sensitive nature. So obviously early diagnosis and intervention is gonna be very important.
00:17:51
Speaker
and In terms of the use of biomarkers and blood cultures, where do we stand today with the recommendations? Yeah, thanks, Sergio. You know, two things, I think, when it comes to sepsis diagnosis and quotation marks, we're on a podcast, you can't see me do the quotation marks in my hands. But, you know, I, as Hallie mentioned, I, we, I co-chaired the patient and family partnership group that we're associated with the surviving sepsis guidelines. And even beyond, like, you're you're not going to diagnose sepsis early unless you screen for sepsis. And, you know, each of the patient family partners,
00:18:21
Speaker
all had a story, their journey with sepsis. And you could date each of them back to the fact that they probably weren't screened for sepsis or sepsis was not diagnosed early enough and and might have improved their outcomes, limited the impact of critical illness on their trajectory and their lives if it had have been. And so, you know, we have both recommendations for screening and you can see ones that recommending ah certain tools like NEWS and MUSE and SERS over QSOFA, which, although had some data earlier on, perhaps less robust data compared to the others when it comes to screening. And then also, so the importance of early screening, you know, is crucial when it comes to then to your question around the diagnosis of sepsis,
00:19:05
Speaker
We also you know provide some recommendations around blood cultures, which is still incredibly important, and biomarkers. And you know the biomarkers piece that you bring up, I was in the room for these debates, and they were widespread and robust. And you know there's a lot of excitement around biomarkers, justly so for the diagnosis of sepsis. And no doubt, Sergio, I feel like this is going to be the future, right? Is that five years from now, 10 years from now, 15 years from now, we very well might be able to translate sepsis from a clinical diagnosis to a biomarker-based diagnosis. But the reality of the situation is, at least, and we did these robust reviews informing it, looking at MDW and other novel trade-based, industry-based diagnostic tools, is that the data is just not quite there yet to recommend for one of these novel biomarkers to diagnose sepsis. And so we recognize that sepsis is still a clinical diagnosis. It's not that we're going to take one biomarker and be able to decide on diagnosis for sepsis. And, you know, there's promise from these biomarkers, but but we require further research, further investigation, looking at diagnostic test characteristics before we're at a point that we can recommend for these.
00:20:13
Speaker
Could you comment on blood cultures and what is recommended today, just as a reminder for everybody? Absolutely. So anybody with, you know, probable definitive sepsis, the recommendation is to send for blood cultures, ideally before antibiotics, but but it's not necessarily absolutely the case if if it's going to decrease the time, you know, inappropriately delay the time to antibiotic administration, especially in that golden hour, it not to defer. But if you can, send blood cultures before, but certainly to send blood cultures for all patients with suspicion for sepsis.
00:20:53
Speaker
What about blood lactic measurement?
00:20:58
Speaker
Absolutely. So still recommended for blood lactate measurement in patients with sepsis. You know, i believe it's a conditional recommendation. I have them up in front of me.
00:21:11
Speaker
Lactate is not a perfect measure by by any means. And there are definitely patients with evidence of sepsis or hypoperfusion that don't have elevated serum lactate. And there's we can perhaps discuss targeted resuscitation around normalizing lactate levels when we get to the hemodynamic subgroup. But there's there's no doubt that lactate can be one of those pieces of information that can help in terms of guiding even initial fluid resuscitation, as well as diagnosis. And so we do make a recommendation for measuring lactate for sure.
Debating Fluid Recommendations and Antibiotic Timing
00:21:41
Speaker
One of the, i would say, more more debated or controversial over the years a commend recommendations relates to initial fluid resuscitation. And we will talk about hemodynamic management a little bit later, but and but this is in this section and the in the guidelines. Could you talk about that?
00:22:01
Speaker
Sergio, you know, it's, listen, always, I hope Hallie doesn't mind me saying, but probably the the most controversial and talked about recommendation in the entire guideline is the, you know, evil 30 mils per kilo. And perhaps I shouldn't do it, but inevitably end up going on social media after the publication of the guidelines. And no doubt, I mean, I think it's important to understand the the criticisms that are out there and and appreciate that the diversity and perspectives and but But, you know, we had a lot of discussion as a guideline panel around these these recommendations around 30 mil. And I think that there's been important evolution over years. You know, this was a strong recommendation in the past, maybe more contextualized now as a a conditional recommendation meant that it's a
00:22:43
Speaker
It's meant to apply to most, but but certainly not all. And there there is data to support you know sufficient fluid resuscitation. And perhaps some of the more recent trials, you know this has now been indoctrinated. It's it's part of what we do. and And by no means are we, again, especially with the conditional recommendation, suggesting that all patients and need this exact amount, but that there's something magical about 30 mls per kilo. And you'll notice that there are a number of remarks that specifically follow this process.
00:23:12
Speaker
recommendation, consideration for individual patient characteristics in selecting the initial fluid volume. Clinicians should perform frequent ongoing reassessments and closely monitor patients to avoid harms and under over resuscitation. And that that it should be weight based, based on ideal body weight and specific considerations in those with elevated BMI. So, you know, again, i think it's important to acknowledge that patients with sepsis most often require an initial fluid resuscitation. And you know barring some better number, this is still what's framed within the guideline, but those considerations should not be ignored and need to be incorporated into any contextualization of this recommendation for sure.
00:23:55
Speaker
And I believe a lot of the pushback also comes from misunderstanding of what the guidelines are intended to do, which is guide, right? And give ah general information for what would appropriate for most patients, but always use at the bedside your clinical acumen and try to individualize the care for that patient that you are dealing with.
00:24:16
Speaker
That's such an important comment, comment Sergio. 100% agree. And, you know, it's it's tough to make guidelines that are meant to be applicable in academic centres, community centres within the United States and Canada, beyond low-middle-income countries, where there's an intentional commitment to applying these recommendations in the low-middle-income setting as well. And so, you know, perhaps... Perhaps if you're at a site with advanced hemodynamic monitoring and POCA skills, and you know there might be different knowledge translation and application of some of these recommendations compared to other settings. But but within those challenges, trump trying to come up with recommendations that are globally applicable, again, we followed a comprehensive process and did our best. And exactly as you said, these are meant to be guidelines, especially conditional recommendations, Sergio. They're meant to be considered and applied within the context of the patient in front of you.
00:25:07
Speaker
Excellent. Haley, I would like to shift the gears to infection management, which obviously is a center point of our care for sepsis, and start with a timing of antibiotic initiation in the hospital.
00:25:22
Speaker
Yeah, absolutely. So the antibiotic ah timing recommendations, these are summarized in figure two of the guideline. And I would say that these are generally, you know, completely consistent with the 2021 guidelines. You know, there's some you know sort of small tweaks to language, again, always trying to be sort of more clear and concise as able, but really consistent with previously. So if sepsis is definite or it's probable, meaning it's your leading diagnosis, you should administer antimicrobial therapy immediately, ideally, you know, within an hour of recognition. and then when sepsis is possible, this means, you know, you have a moderate so suspicion, but you're also entertaining and evaluating other diagnoses.
00:26:01
Speaker
The sort of next steps are really recommended to be stratified based on how sick the patient is, right? So if a patient is in shock, this is really, you know, too sick to guess wrong. So the recommendation is administer antimicrobial therapy immediately. Of course, you know, continue to look for other causes, you know stop those antibiotics if it turns out to be something else.
00:26:21
Speaker
um But then in patients you know who are less sick, shock is absent, sepsis is possible. We recommend a rapid assessment of infection versus non-infection causes of illness with this goal to administer antimicrobial therapy within three hours if concern for infection persists. So this is really trying to carve out time to do you know additional history, additional physical exam, you know x-rays, ultrasounds, blood work. There's typically you know a number of additional things that can be completed within that time window that are going to allow you to either increase or decrease your pretest probability, like how likely is it that this patient has bacterial infection, and then make a more informed decision about whether to prescribe antibiotics. And so I would say at a high level, right, this framework is really trying to balance two things. One, the urgency of treatment that we know is particularly present in patients presenting with hypotension and shock.
00:27:17
Speaker
um But then also being mindful about over treatment and not, you know, just sort of treating everybody across the board. So that's really the sort of intention behind that framework. Absolutely. And I do believe that just to reemphasize the the likelihood of sepsis being the diagnosis and the severity of our patient are going to probably push us to earlier and broader.
00:27:39
Speaker
and and And this is not meant to to mean that you have an elevated white count and everybody gets antibiotics, right? Which I think has been the way some people have interpreted this over the years and has led to maybe over usage of antibiotics with all its potential complications.
00:27:57
Speaker
Yeah, exactly. Right. In terms of empiric antibiotic coverage, there there are three areas that I found ah quite interesting and and worth
Antimicrobial Stewardship and Antibiotic Reassessment
00:28:08
Speaker
discussing. If you could comment on antibiotic coverage, which is empiric for md potential MDR pathogens, multi-drug resistant pathogens, antifungal em period coverage in anaerobic and empiric coverage, coverage.
00:28:24
Speaker
Yeah, absolutely. Yeah, I would say like in general at a high level, I think the evolution that we're seeing in the guidelines is really having this kind of greater focus on antimicrobial stewardship during that kind of like initial time when you're selecting the empiric coverage, right? Because there's sort of two things you're trying to do. One, you want to cover the likely pathogens. But I think there's also increasing recognition that, you know, when you treat with kind of broader than needed antibiotics, not only are there these kind of like theoretical harms that can happen in terms of, you know, you know, promoting antimicrobial resistance, but there's also like direct kind of
00:29:02
Speaker
harms that it can occur to the patient due to this kind of off-target coverage. So this kind of comes out, I would say, most clearly in the anaerobic coverage. And these are brand new recommendations. Like this was not a PICO question that was addressed in prior guidelines.
00:29:16
Speaker
um But ah we asked about... um empiric antierobic coverage And there's really like emerging data showing that for patients with like a very low likelihood of an anaerobic infection. So for example, lung infection or a urinary tract infection, it's very unlikely that those sites of infection are going to be caused by an anaerobic pathogen. And in those instances, treatment with empiric anaerobic coverage is associated with worse outcomes, right? So like increased mortality, and this is really thought to be mediated by um disruption and depletion to the healthy gut microbiome. That's like an incredibly important, essentially, organ and is important for um resisting infection. And this is, you know, there's also like a wealth of preclinical evidence that also kind of supports what's also been observed. in in in human patients So we now have these paired statements, a conditional recommendation to avoid empiric anaerobic coverage in patients with a low risk of anaerobic infection, and then to include anaerobic coverage in patients at high risk. So this means like... If it's a lung infection, if it's a urinary tract infection, avoid anaerobic coverage where possible. By contrast, you know if it's intra-abdominal infection or a necrotizing infection or this deep-seated gynecological or obstetric infection, you would want to cover for anaerobic pathogens. and And when you think about implementing this recommendation, it's not only about like, oh, gosh, well, should I add something like, you know, metronizol or clindamycin, these things that are prescribed very specifically for their anaerobic coverage. It's really also about trying to be mindful for the gram-negative coverage that we're prescribing because there's huge differences in cross-antibiotics prescribed per gram-negatives in terms of whether they also come part and parcel with anti-anaerobic coverage. So for example, peperacillin, tezobactam, you know, has, you know, very strong coverage against anaerobes where, you know, cefepime,
00:31:13
Speaker
does not. And so it's sort of just adding this to the conversation to, you know, sort of think about being mindful of that, avoiding it where feasible, you know, while of course still being, you know, mindful of your hospital antibiogram and, you know, sort the resistance patterns and the, you know, populations that you care for.
00:31:31
Speaker
um And then this sort of same, I would say just high level, you you know, theme of, you know, treat what's likely and try to limit treatment and what's unlikely. We see the same thing, you know, for MDR pathogens. So, you know, you want to sort of limit your MDR pathogen coverage to patients who are at higher risk and avoid that coverage in patients who are lower risk for any particular MDR pathogen.
00:31:55
Speaker
And then antifungal coverage, this one's also kind of interesting. So previously we had paired statements in the 2021 guidelines, like, you know, include it for high risk patients, but like avoid it in low risk patients. But think the issue is that even in high risk patients, right, clinical trials enrolling patients with hospital onset sepsis, you know, in theory, you know, high risk for um antifungal infection, even those types of trials that are really trying to zone in on the um and target the high-risk patients do not find benefit of empiric antifungal coverage because this is you know quite rare and we don't have sort of great tools at present to identify who are the highest risk patients to be able to provide that And I think like the the the the guidance is really evolving there. So the suggestion, conditional recommendation is to not provide empiric antifunnel coverage, but then we have a remark, you know i mean? and This can be considered on a case by case basis. And it's it's really trying to sort of match the guidance with how commonly you might do something in practice. practice. So, you know, with these kind of two conditional recommendations, it might be like, oh, you know, most of the time I don't, but maybe a third of the time I do. And it really should probably be less than that, right? More on a case by case, very sort of, um you know, less commonly should we be including that antifungal coverage. And so the guidance has really evolved that this is now really covered in a remark, as opposed to our own sort of
00:33:25
Speaker
conditional statement regarding antifungal coverage. So hopefully that sort of demystifies maybe a little bit like how we, how those, you know, those, you know, the guidance has evolved over time. and And I personally really like the the the use of the remarks and because it helps you really define a little bit better who would be high risk and and really and and i encourages clinicians to think at the bedside, right? I mean, yeah it's not to say you do one thing for everybody, but i mean, you should be thinking, is this patient at risk for anaerobic? Is this patient really at risk
00:33:59
Speaker
for for a fungal infection. And in those cases, and if they're in shock especially, I would be more aggressive. So I love that. So thanks for for clarifying that. Oh, yeah, yeah. Thanks so much for the comment. i mean, this is honestly what you spend so much time in that in-person meeting discussing is really trying to finesse, right? Like if your recommendation becomes a whole paragraph, you know, you've kind of lost. And so it's really trying to keep those recommendations short, but then, yeah, add this more nuance, kind of like nudge people towards what are the things you should be factoring in when you make this decision at the bedside for, you know, the individual you know patient right in front of you or taken care of. So, yeah, that's really the goal and that's what we sort of strive to do. And so, yeah, hopefully those remarks are helpful to people. Absolutely.
00:34:40
Speaker
and We don't think, and when when I say we, I'm talking about physicians and especially probably that much about pharmacokinetics, pharmacodynamics, but our clinical pharmacist colleagues do a lot. And there was a very strong recommendation for the administration of beta-lactam antibiotics. Could you talk about that?
00:35:00
Speaker
oh I think you're talking about the strong recommendation for prolonged infusion. is that right? Correct. Yeah. Yep. So this was upgraded. So this was a conditional, um you know, ah we suggest during the 2021 guidelines, and this was upgraded to a strong recommendation. And And really the the basis for upgrading this is that there's now, you know, several clinical trials, high quality. So you're bringing together multiple, you know, high quality ah clinical trials and showing that there's a mortality benefit. And so that's really, you know, this kind of, you know, Higher certainty evidence is what's bringing the the strong recommendation. and and the And the rationale for this is that, you know, after that initial ah rapid bolus loading dose to kind of get your drug levels up, use of prolonged imprusions, you know, has better, you know, essentially โ
00:35:52
Speaker
pharmacokinetics, pharmacokinetics, then doing these kind of intermittent bolus infusions. And so this maintains your, you know, drug levels at a safe and effective ah dose for a longer period of time.
00:36:04
Speaker
And then again, bears out that this is associated with the most important, you know, improved mortality improvements in patient important outcomes. So yes, this is now a strong recommendation and overall summarized as being moderate certainty evidence.
00:36:19
Speaker
we We tend to start broad, especially in sicker patients, and we tend to love to keep our antibiotics going on forever as intensivists. Could you talk about de-escalation and discontinuation of antibiotics?
00:36:33
Speaker
Yeah, absolutely. So there have been, you know, like a number of recommendations on this, you know, very topic over the years. Right. So 2021, you know, we have recommendations that this should be essentially assessed on a day by day basis. You know, in general, we suggest shorter or longer durations of treatment.
00:36:49
Speaker
You know, now we have a strong recommendation that when the cultures come back, you know, you should deescalate. um And that means either sort of narrowing the coverage, you know, maybe switching antibiotics or, you know, dropping antibiotics that are no longer necessary. So I think in day to day practice, essentially, the antibiotics should never be kind of like a set and forget. This is something that you should review each and every day of like, do they still need what they're on? You know, is there something that can be stopped or discontinued or switched to sort of narrow the spectrum of coverage?
00:37:21
Speaker
Anything else you want to add with antibiotics before we move on to hemodynamic management? um no i think No, I think we're good. I think we covered the key aspects there. Yeah, thanks. Excellent.
00:37:32
Speaker
Ram, I would like to talk about hemodynamic management, which obviously could be a podcast on of itself, and like many of these topics, but really encourage all our listeners to read the paper, but also look at figure three, which I think summarizes is the management and all the recommendations very nicely.
Monitoring and Fluid Management in Sepsis
00:37:52
Speaker
But could we start by talking about blood pressure monitoring and target and blood pressure in terms of the map?
00:37:59
Speaker
Yeah, great, Sergio. would Totally agree. This was the working group that I sat on formally, and we had some great discussions. It was always a bit hard with scheduling because we had members from across the world. So I can think of many times sitting in my house in the basement at five zero in the morning or six in the morning having passion discussions about hemodynamic management and sepsis, just given the realities of the time change and making sure that we had as many folks as could be there. You know, i This has obviously evolved a fair bit over time, the idea of invasive versus non-invasive blood pressure monitoring in patients with septic shock.
00:38:32
Speaker
And, you know, the the discussions were heated already around the necessity of having arterial access versus using non-invasive. And you're probably very aware of the the New England Journal study results from the Everdac study that was published, you know, sort of well the manuscript was in process, we definitely incorporated this into our considerations, but didn't really change the sentiment of the recommendation. Recognizing that, you know, there's probably a role for both as, you know, non-invasive or invasive and individual patient factors can likely influence that. And you'll see that reflected by the fact that we made a conditional recommendation for using either invasive or non-invasive blood pressure monitoring. There's a few considerations in the remark here. Again, you know using those remarks to our advantage as much as possible, talking about those on high-dose vasopressors, escalating doses, multiple vasopressors, the need for frequent arterial blood sampling might all be reasons why one might think about placing an arterial line. But...
00:39:31
Speaker
you know, the given the potential for complications, pain for patients, all those other factors, recognizing that it's not the be all and end all. And certainly based on study results, it doesn't change outcomes. I think this was most impactful for the folks because it's part of what who we are as intensivists. It's what we do. We put in lines and we monitor patients closely. but But I think it's inherent on all of us to reevaluate some of those fundamental features that we we take for granted within the ICU in evaluating practice and and seeing you know what's best in terms of improving patient outcomes at the same time.
00:40:07
Speaker
And in terms of the MAP, there's also new recommendations for the target. Could you talk about that? Absolutely. So, you know, listen, i feel like similarly, the challenging topic, similar to the 30 mils per kilo, there's, there's you know, 65 is a relatively arbitrary number in terms of map targets, you know, and and I think that there's recognition that that that is the case. We certainly still kept...
00:40:31
Speaker
that number for the majority of patients, but recognized that it's impossible to target exactly 65 and suggested that a five millimeter mercury variance may be between 65, 70. Again, a conditional recommendation is most appropriate for the majority of patients. but But again, a conditional recommendation to suggest that there might be a subset of patients for which this doesn't apply. We made a specific a second recommendation for those over the age of 65 based on Francois LaMontagne's 65 trial in JAMA, showing potential benefits of slightly lower map targets in older adults.
00:41:04
Speaker
But there's still ongoing uncertainty in this area, Sergio. And, and you know, the a reassuring part is is that we're going to have more data addressing optimal map targets in the in the coming years. You're aware perhaps of this mega map ah randomized control trial currently enrolling led by Paul Young and the Australians and then Francois Lamontagne also doing ongoing work around optimal MAP targets. So, you know, we have what we have for now and I think it's reasonable and probably consistent with practice in terms of what most folks do aiming for, you know, somewhere in that 60 to 70 range depending on perhaps some other patient related factors around age and and others. but But I think that we'll we'll have more data addressing this question soon.
00:41:44
Speaker
Perfect. Fluids, another topic that we've been talking about for for a long time, right? And it seems to go in like a pendulum back and forth. But we do have more data over the last couple of years. And could you talk about the fluid type com recommendation?
00:42:00
Speaker
and thats And then a little bit about albumin. Yeah, absolutely. Maybe we'll start crystalloids versus colloids because I think it's a ah good centering debate. You know, we haven't touched the recommendations around starches and gelatins from previous iterations. There's not really new data we made strong recommendations against, and I think that's consistent with current practice as well. The albumin one has shifted a bit, and and again, passion discussion within the room of of the surviving sepsis experts around the role of albumin. You know, when you look at systematic reviews of the data that's out there, there's certainly no evidence of harm, but but at the same time, also no evidence of benefit.
00:42:37
Speaker
And a lot of the point estimates when looking at a number of the patient important outcomes fall right on the line of no effect. And so a lot of the discussion, again, centered around the fact that you're unlikely to cause harm by giving albumin, but at least, you know, taking that low middle income perspective, thinking about costs, choosing wisely, the rationale behind administering an intervention that is much more costly compared to crystalloid without evidence of benefit becomes contentious. And so that's what informed the conditional recommendation against crystalloid giving supplemental albumin. Now, if you told me, Sergio, that you were running a randomized control trial, specifically looking at the role of albumin, perhaps some recipe of albumin and crystalloid, would certainly be willing to randomize my patient again, recognizing that there's probably unlikely harm. But at least for the practitioners reading this guideline, you know, without further data supporting the rationale for administering something that's much more expensive, I would say stick with crystalloid in the majority of patients. And that's Certainly consistent with the recommendations that we made. Now, when it comes to which crystalloid, oh my goodness, what a long history of, you know, we, I'll tell you prior to 2010, 2015, nobody really cared about this crystalloid debate or the discussion about which crystalloid was optimal. But We sort of recognize that normal saline, again, using my invisible quotation marks that you can't see is far from normal, has a chloride and sodium concentration much higher than that of human plasma. And so the rationale goes is that perhaps balanced crystalloid is able to get away from some of these complications like hyperchloremia and metabolic acidosis and might be more beneficial.
00:44:16
Speaker
You can look at the largest randomized control trials, BLAS, BASICS. They don't show an improvement in patient-important outcomes like 90-day mortality when using balanced crystalloid. But when you do the and individual patient data meta-analysis and use a Bayesian approach, there's maybe a signal once you pool all the data together of a slight benefit of balanced crystalloids. When I say balanced, I mean those ringers, lactates, and and plasma lights of this world. And so... That's what informed the conditional recommendation to use. You know, also, again, from the low middle income perspective, the cost is about the same between balanced crystalloids often in in many jurisdictions and saline. So we felt like it was okay from that perspective. Maybe as a little teaser, Sergio, I'll let you know that we just completed a randomized control trial specifically looking at ringers versus saline in patients with septic shock. We're going to be presenting the results at CCR in Belfast in June. So, you know, maybe... further data that could be incorporated into subsequent versions of surviving sepsis.
00:45:12
Speaker
Excellent. And we'll definitely, I mean, have you back to talk about that post-June. So what about hemodynamic monitoring and from the perspective of fluid resuscitation guided by measures, and so serial lactate measurements, and capillary refill time? And then I have a ah question for the my POCUS crowd friends.
00:45:34
Speaker
I feel like, you know, even with the previous iterations of the guideline, we've moved away from the static measures of of hemodynamic response to fluid administration. Those CVPs and swan GANS catheters have quickly become less used in our unit and have more focused towards some of these dynamic measures like passive leg raise and systolic pressure variation, a pulse pressure variation. And so you'll see, again, a conditional recommendation for using these dynamic measures to guide fluid resuscitation. Certainly in those with an elevated lactate at baseline, targeting fluid resuscitation to to improving lactate clearance, again, consistent with the previous recommendation, we said, hey, if your el lactate is elevated to start with, try and normalize that lactate or target normalization of lactate with fluid resuscitation. The the cap refill one,
00:46:25
Speaker
I also find interesting, I was actually just speaking to a few students about this earlier, is that despite building evidence, I still feel like it's probably underutilized in most centers. I'd be curious to hear if either of you use routinely cap refill when targeting and guiding resuscitation in your patients. Now, Maybe things like Andromeda 2 that have recently been published, building on Andromeda 1, demonstrating the benefits of using ah a protocol that incorporates cap refill will help change that paradigm. You'll see we made a conditional recommendation for using cap refill time as one of your tools to guide fluid resuscitation. But I don't know what the operational barriers are, but I still find that that it's not used widely. Maybe I need to commit even with my own practice of of using it more. I guess, you know, Sergio, there's probably not one tool that folks will use to guide their fluid therapy, but some combination of these dynamic measures, cap refill, lactate clearance, is and and precipitated around the idea of a test bolus looking for improvements in these parameters is probably the optimal way to go and and recognized in the recommendations.
00:47:29
Speaker
So point of care ultrasound, obviously, at least in North America and Europe, has really taken it off in the ICU. and I understand kind of the perspective, but a lot of POCUS fans were kind of surprised that there's not a formal statement that says that use POCUS and you will save every patient with sepsis. Could you comment on that?
00:47:50
Speaker
Yeah, no, and and listen, I use POCUS as part of my everyday practice as well, and I know that there's a role in using POCUS as part of our our toolkit in guiding therapy, and again, Andromeda 2 will help support that idea that there is there's benefit incorporating it as part of it. You know, Andromeda 2 aside, despite the fact that and another one of these interventions that we think it makes intuitive sense that using this to help guide fluid resuscitation will improve outcomes, that there's there's not...
00:48:18
Speaker
the robust ah RCTs that are maybe addressing this. And you know, it's it's it's not prioritized, at least within this guideline iteration, as one of our PICO questions of interest to explicitly address the role of POCUS. But listen, between you and I, I could certainly see it being prioritized as a question for subsequent surviving sepsis guidelines, especially as the uptake and use and incorporation into study protocols has has increased over the last few years. so Certainly, to those focus enthusiasts out there, I would say, you know, there's there's there's building data, obviously. i don't think any of the recommendations that we provide here are are against or not consistent. And, you know, one could consider grouping it as one of those dynamic measures of ah guiding fluid resuscitation and, and you know, ah keep an eye out perhaps for for subsequent iterations of surviving sepsis as that evidence-based builds. I wouldn't be surprised if we see it incorporated more formally.
00:49:12
Speaker
Perfect.
Vasopressor and Corticosteroid Use in Sepsis
00:49:14
Speaker
In terms of vasopressors and ninotropes, could you comment on the timing of initiation of vasopressors and then tell us what the recommendations are for first line, second line, and third line agents?
00:49:26
Speaker
Yeah, of course. You know, the figure three, I think you made reference to is a really helpful tool. I think Hallie put many hours into creating this figure, but but I'm glad that she did because it's a it's a helpful guide and, you know, recommendations are one thing, but when you have 129 of them, having a quick reference point, always helpful, something you can print up, perhaps put in your units or or on display in a clinical area. could be helpful. And so, you know, no doubt you'll see within the recommendations is that that we did recommend for fluid administration ah prior to vasopressor initiation, but there is a remark clearly there that, you know, for some patients, you don't have the luxury of waiting. Those with fluorid hypotension that present quite sick, sometimes this has to be done synchronously in terms of administrating fluid and vasopressors. but But if the luxury is there, then one should at least start with fluid therapy before initiating vasopressors.
00:50:21
Speaker
When it comes to vasopressors, again, not a lot of change, Sergio, since the last iteration. We have pretty clear data that norepinephrine is beneficial as first-line vasopressor across shock states, but but definitely in septic shock.
00:50:34
Speaker
A lot of it, you know, when you compare it in those old CAT trials to epinephrine and the VAS trials to vasopressin, dopamine, and the SOAP trials, a lot of it came down to not necessarily improvements in mortality outcomes with norepinephrine, but less tachyarrhythmias compared to epinephrine, dopamine. That's a lot of the rationale behind using norepi as our first line, and you can see a consistent, strong recommendation for using norepinephrine first line vasopressor.
00:51:00
Speaker
When it comes to second line, there's probably increasing data for vasopressin. And my practice has actually shifted in the the last few years as perhaps having a lower threshold for initiating vasopressin. You might look at some of the trials that have have examined supplemental vasopressin in addition norepi, demonstrating initially folks thought it might reduce mortality, might improve acute kidney injury, and it didn't. But that being said, you know, when you pool estimates together, maybe an impact on some of those important outcomes. Most importantly, adding vasopressin leads to less tachyarrhythmias. And again, that's quite clear based on there was a meta-analysis in 2018 in JAMA that showed that. my you know we make a recommendation for starting vasopressin as a second vasopressor with increasing norepinephrine requirements there's one of those in your practice um in our practice around what threshold folks use for initiating vasopressin but but again i'll be honest with you my my practice is that it's certainly dropped in the last little while it's lower doses of norepinephrine i'm thinking about adding baso and especially with that rationale of of less tachyarrhythmias And when you start getting now down to third vasopressor, you know, we made a recommendation suggestion, conditional recommendation for epinephrine. Certainly, this is the case where you're you're running into a very high mortality once you're starting to initiate three different vasopressors.
00:52:23
Speaker
Excellent. Any comments on inotropes?
00:52:28
Speaker
Even in those with suspected ah cardiac depression, there's still a recommendation for initiating starting with norepinephrine. The the recommendations of a around vasopressors make life easy, right? Is that you have a patient with shock in front of you, for most indications, you can start with norepi. A lot of the trials that examine the optimal vasopressor included patients with shock of any etiology.
00:52:48
Speaker
think we said within the recommendations, you could consider norepi or epi as first line in those with septic shock and comorbid cardiac dysfunction. If despite norepinephrine or epinephrine as vasopressor, as we both know, they provide some inotropic, conotropic support as well, you're still not achieving lactate clearance or adequate perfusion. We did make a recommendation for adding inotrope support at that time and either dobutamine or milrinone. There was insufficient evidence to make a recommendation for one or the other.
00:53:21
Speaker
And there's been a lot of talk in the literature, well, not in the literature, a lot of, think, discussion among intensivists on using metadrine in different contexts and also methylene blue in multiple contexts with shock.
00:53:35
Speaker
What do the recommendations say on these two? There has been increasing discussion on both. And, um you know, you see variable practice when it comes to both as well. Even in my center, I see variable practice when it comes to midadrin. And, you know, when it's midadrin, there's the role perhaps in those that are on vasopressors, active vasopressors still in the resuscitation phase. And then some advocate for using midadrin in the de-escalation phase. helping to come off those that are on decreasing doses of vasopressors, especially the motivation there may not be improvements in outcomes, but if you're able to liberate a patient from vasopressors sooner, you might be able get them out of the ICU, which could be important from a systems perspective and cost effectiveness perspective.
00:54:17
Speaker
you know Unfortunately for both agents, the data is not quite there sufficient enough to provide recommendation recommendations for either. We did discuss ah quite a bit ah related to both. But again, reassuringly, Sergio is i'm avidly aware of ongoing randomized control trials, both Canadian-led and others, that are addressing both interventions. and so Hopefully we'll have a little bit more guidance around each of these in in the coming years. And who knows, hopefully within the subsequent surviving sepsis might have data to inform recommendations. It wasn't for a lack of trying this time. we did we did do systematic reviews. we We chatted through things, but felt like that there wasn't enough out there to to provide recommendations.
00:54:59
Speaker
Perfect. I would like to to switch gears and talk about adjuvant and supportive therapies. Hayley, could you make the comments on what is the most current recommendation on corticosteroids?
00:55:12
Speaker
Yes, absolutely. So um very consistent with prior, we have a conditional recommendation, a a suggestion to use intravenous corticosteroids in patients with septic shock.
00:55:24
Speaker
um I think there's a lot of aspects about sort of steroid treatment that that people wonder about, like when do you start it and what dose and like, should you also be using flutocortisone and like, when do you stop it? And so it's really hard to prioritize all of those many questions into the guideline. And so we tried to, you know, give a little bit more information beyond just this conditional recommendation to use it in septic shock through these in our practice statements. So we have almost like a full paragraph sort of describing, you know, how the panel is currently using it, you know, whether as an intermediate, ah intermittent dose, which is what most people are doing versus a continuous infusion. you know, at what sort of threshold of norepinephrine equivalents people are starting at or sort of after how much time on basal pressors and then whether people are using flutocortisone and how they're stopping it. So again, hopefully that provides more information, but yeah, guidance is really consistent with prior, you know, suggestion to use this, you know, appears to definitely shorten duration of shock and, you know, may provide mortality benefit as well.
00:56:26
Speaker
Perfect. Any comments on antipyretics? Yeah, so this was interesting. You know, you're always trying to sort of address new questions in the guidelines. And so this is something that had not been previously discussed.
00:56:40
Speaker
you know addressed previously. And so we were looking very specifically at the use of antipyretic therapy for the purpose of and you know improving patient important outcomes. right These are things like mortality, duration of shock, vent-free days, things like that. And there's really not evidence that antipyretic therapy does that. And so we're pretty careful in the wording of this recommendation. right So this is a conditional recommendation, a suggestion against the use of antipyretic therapy um or surface cooling for the purposes of including improving clinical outcomes. But of course, you know, if there's kind of like, you know, symptom control issues, you know, you can sort of still use it on an as needed basis, but essentially just says like systematically, you know, like sort of managing temperature at a certain level for all patients with sepsis, you know, doesn't seem to, you know, confer patient, you know, improvements in patient outcomes that we can identify in the literature thus far. And I'm going to lump in several treatments together here because the recommendation is the same.
00:57:42
Speaker
and Yeah. Which are vitamin C, IVIG, vitamin D, and blood
Evaluating Emerging Treatments and Practices
00:57:47
Speaker
purification. Could you just make a comment on these? Yeah, so these are all things that we look into, you know, for the guidelines, you know, really, we have suggestions against all of these things. I will say the one area that is probably different in an area of kind of more active research and where things could change in the future is, is um you know, blood purification. i think it was like pretty much the exact same day that the guidelines came out. This TIGERS trial was released in Lancet Respiratory Medicine. and so again, this was, you know, looking at a very specific population of patients with septic shock and a high endotoxin activity and multi-organ failure. but did find that this treatment was associated with a high probability of mortality benefit. So it seems like maybe there's like very select subgroups of patients who may benefit. Of course, we did not have that data available at the time that we did the review.
00:58:38
Speaker
um So I would say that, you know, vitamin C, IVIG, you know, vitamin D, all of those we suggest against, and I'm not aware of a lot coming down the pipeline. Blood purification is absolutely something that feels like more of an evolving field. And it may prove to be that there are, you know, very select groups of patients for whom there may be benefit and we'll have to address that again, you know, in future guidelines.
00:58:59
Speaker
And the last therapy I wanted to ask about was active fluid removal, which I understand is a new recommendation. Yeah, absolutely. So we have a conditional recommendation, a suggestion to use active um fluid removal or de-resuscitation in patients after sepsis resuscitation. and And to be honest, this was an area where I think we really kind of heard the the patient voice come through. And I think we even sort of, you know, mentioned this in the presentation.
00:59:29
Speaker
in the narrative write-up yet. It says, our suggestion for active fluid removal was influenced by input from patient representatives who placed a very high value on avoiding edema. So I don't know, in clinical practice, this comes up all the time, right? Patients and families asking like, you know, why the edema, why swelling? And it's it's very... um You sort of bother some to patients, you know and I think there's also, you know, some data that it also, you know, impedes functional recovery. And of course, that makes good sense if you're sort of carrying around extra weight and it's already hard to, you know, get up and moving after septic shock. So that certainly, you know, influenced when we sort of think about how the, you know, the patient values, um you know, come in through that evidence to decision framework. So, yes. New ah conditional recommendation. And then, um you know, we have, of course, more remarks on this one, too, where we talk about what this looks like, you know, so typically this would be diuretics.
01:00:21
Speaker
um But if that's not effective, then there are other you know means like through ultrafiltration. And then a number of different factors that we point out to consider. when thinking about active fluid removal, including cardiorespiratory function, vasopressor dose, sort of like are they at a point where it's safe to start de-resuscitation, and then also looking at things like the exam, peripheral edema, weight, fluid balance to determine patients who may benefit.
01:00:47
Speaker
Excellent. as we As we close our discussion, i wanted to and pose a question to both of you. And then we'll start with Hallie. Most impactful new recommendation in your opinion. This is impact at the bedside.
01:01:02
Speaker
Yeah, so for me, I think it's probably these new recommendations related to the anti-anaerobic coverage. And I think that's because it's just sort of like a new area, these kind of off-target effects of antibiotics in the microbiome, I think is something that's, you know, really emerged of recent, um um has certainly influenced my clinical practice, and I think ah very important to patient outcomes.
01:01:27
Speaker
Ram? and I thought long and hard about this one and I think I have to go back to the hemodynamic subgroup which is maybe biased by but the one that I had the most passionate discussions around and and perhaps around this invasive versus non-invasive blood pressure monitoring. i don't know where the pendulum is going to land and what's best because I fully support the idea yeah that there is still a subset of the population that we need to make sure that we have invasive arterial monitoring. You know, the other caveat to this is that we talked with our patient family partnership group and those that had experienced septic shock. And, you know, from a patient perspective, things could go both ways is that having a cuff going off every five minutes also could be very uncomfortable. And some patients express that there might be a preference actually for arterial cannulization, but then granted that the actual process of
01:02:15
Speaker
placing the arterial line can be painful and expose patients to complications related to that as well. And so I like the recommendation that that goes both ways, but it will be it will be interesting to see how that evolves over time. And maybe if I can sneak in a second, I also like the idea of moving perhaps a little bit away from administering albumin and a conditional recommendation against, you know, this again, early in my career, I probably used much more albumin supplementation in patients with sepsis and septic shock. However, recognizing and having participated in these evidence synthesis, understanding the differential in cost and lack of clear benefit, i've I've certainly moved towards using less and find this updated recommendation more consistent with my practice as well.
01:02:58
Speaker
Excellent. The second question is most important or impactful old recommendation as a reminder for all our listeners from previous
Emphasizing Early Diagnosis and Expert Insights
01:03:06
Speaker
guidelines. And we'll go first with you, Bram.
01:03:10
Speaker
oo Good question. You know, I think it comes down to sepsis screening. and And again, this was the common theme heard from our patient family partnership group is that if only the clinician had thought about sepsis early on, because we all know as a syndrome, it presents in so many different ways. And we know the importance of that golden hour, few hours and immediately following diagnosis around ah early administration of antimicrobials and and fluid resuscitation if if needed as well. And so I think that the main recommendation that that jumps out in my brain having participated in that and for so many is the importance of of screening all of our patients for sepsis in in order not to miss this diagnosis.
01:03:50
Speaker
Perfect. Hayley? Yeah, so great question. And I think for me, it really goes back to the antibiotic timing and also the initial fluid resuscitation recommendations. I think just sort of over and over and over again, right, we learned that sepsis is this time sensitive medical emergency and the faster we can take care of the problem, the better sort of prevent the problems. kind of, you know, downstream progression and complications. And this is actually kind of what makes me, you know, a little bit sad about all the debate about the 30, you know, ML per kg recommendation is because this is really about sort of trying to get on top of the problem and really fix the problem. And the vast majority of patients tolerate, you know, 30 mls per kg just fine. And many of them are then sort of fixed, like blood pressure is stabilized. And so when people kind of push back against this, you know, it'd be like one thing, I'd be totally happy if everybody kind of transition maybe more sooner to a personalized resuscitation approach.
01:04:45
Speaker
But what I'm really concerned, you know, happens instead in clinical practice is that they do this kind of like slow roll, right? Like they give 500 mls, you know, I'll check back on the patient, but then they get tied up in another patient's room. And so the patient kind of smolders along and, you know, like sort of just doesn't sort of resolve the hypotension. and And that's really problematic. And that's really the reason for this kind of pragmatic, you know, upfront treatment. And then for patients, you know, who on a case-by-case basis this have be a lot of risk factors or, you know, prove themselves to be sicker and ongoing hypotension after that fluid bolus, you know, then you can transition to a personalized approach. So I think really, you know, screening like Bram mentioned and then really prompt treatment with antimicrobial therapy and fluid Those are sort of like the golden three things for sepsis management.
01:05:30
Speaker
Excellent. We like to finish the podcast usually with a couple of questions that are unrelated to the clinical topic. Would that be okay? Yeah. Sure. So I'll go with Bram first.
01:05:42
Speaker
Is there a book that has influenced you significantly ah or that you have gifted often to other people?
01:05:49
Speaker
i i appreciate the question. I don't i do a crummy job of of reading either for work or for, I mean, I obviously read a lot for work, but finding time for fiction, nonfiction that that I enjoy.
01:06:01
Speaker
i wish I did a better job. My wife gets into bed every night and reads and I don't know, she's always bragging about it, not bragging, but with the two of us where she's allowed to brag, having read 20 or 30 books a year and i' lucky if I get to one or two while we're on vacation. I guess if there are a a subset of books that I do enjoy, it's it's probably in the nonfiction and a bit of a history of medicine nerd. I love reading about, you know, how we used to practice 50 years ago, 100 years ago, and then learning about all the ways that we became proved wrong, that those were those were silly things to do. And and it looks so backwards now. And I guess the reason I like this and reading about this so much is to
01:06:40
Speaker
think towards 20 years from now, 30 years from now, what folks are gonna look back at what we're doing now and think how backwards we've been practicing and and what we're doing. And I guess when it comes to ah history medicine, one book that had a profound effect on me was the biography of William Osler. He's a Canadian physician, might be familiar with, and, you know, really brought that bedside clinical exam to the forefront.
01:07:02
Speaker
um And not only that, but he was actually born and raised in the same small town in Ontario that I was. So I sort of feel that that connection to him. So if maybe that's my thoughtful response, Sergio, is the but Willie Mosler biography. Perfect. I mean, a lot to learn from William Osler and truly ah a father figure in North American medicine, right? I mean, he practiced, I think, for many years in Hopkins. So for sure, we will include that that link to that biography. Haley, you've been on the podcast before and we've talked about books. So I want to ask you about music today.
01:07:34
Speaker
What music album, and I'm old school, call it an album or playlist, would you want with you in a prolonged isolation period, either on a deserted island or in a new pandemic? Hopefully not. Yes. Great question. Yeah. So my sort of favorite um artist right now is called Monrovia. This guy, so I think his real name is John J. Lowe. He was born in Monrovia in Liberia in civil war and then was adopted into the U.S. And she's got this amazing kind of personal story, but he's an amazing singer. I heard him on the radio maybe like a year ago and then was like, oh, you know, I really like to say, like, you know, jotted down the name so I could look it up. I looked the guy up and then when I was looking him up,
01:08:15
Speaker
it was like tickets go on sale he's coming to ann arbor tickets go on sale in two days and so i got tickets and i saw him i think it was in november and he was just totally amazing lovely guy really sort of compelling backstory so recommend checking out his music i listened to it on repeat awesome i never heard of him but i definitely am am curious now like next question for you bram it tell us something you have changed your mind about over the last couple of years Medicine related surgery or anything?
01:08:44
Speaker
Your choice. Well, maybe I've done lots of medicine and even my book example was medicine related. So maybe I'll go lighter this time around. We're big sports fans, despite being up in Canada, follow NFL and Major League Baseball and everything quite closely. And have ah four young boys, young boys between the ages of 10 and 14. And I guess, you know,
01:09:05
Speaker
ah between following the Toronto Blue Jays and the Buffalo Bills and the Toronto Maple Leafs, I felt like the boys asked me, I say, you'll definitely see a championship sometime in in your lifetime, no doubt. But, you know, the way the Blue Jays lost so awfully last year and the way the Buffalo Bills seem to be so close and and never quite make it, I guess I'm not so sure that my boys will see a championship or one of the teams they like ah in in at least my lifetime. But who knows, Sergio, there's always the beauty of being a sports fan is there's always next year. There's always hope. Yep. So we'll see.
01:09:37
Speaker
i can, I can sympathize with you. i was born in Buffalo and remember the nineties when I think it was four or five Superbowl losses in a row. So who knows, right? Maybe last question and for Haley, what would you want every
Final Thoughts and Tools for Clinicians
01:09:52
Speaker
listener to know? It could be a quote or a final thought to close the podcast.
01:09:56
Speaker
Excellent. Okay. Yeah, i'm going to give two final recs. Okay. So first is that there is a um an app that you can download for your phone. It's SCCM point of care or POC. And so you can download that. And then um it's got the whole surviving sepsis campaign guidelines on it. And so you can, you know, scroll and, and um you know, search by different types. So that's that's it. They're big. There's lots of recommendations, but that's one tool to help you easily navigate and have it at your tool at your fingertips.
01:10:25
Speaker
And then the second is I want to put in a plug for a book. um You guys were talking about books and Bram got that question, but there's a book called Blood Poison, The Untold Story of Sepsis that is coming out this summer. So it's available for preorder now. And i got to read it ahead of time and like do a review for it. And so it was really awesome. The first about half of the book is really just this kind of like ancient history you know, when was sepsis first mentioned in Greek literature and all this kind of stuff and germ theory and antibiotics and kind of all this medical history stuff.
01:10:57
Speaker
And then the sort of second half of the book is all the kind of recent stuff, right? The surviving sepsis campaign guidelines, the, you know, sort of policy fights over SEP1. And so I think it just does a great job of kind of like contextualizing everything and giving this kind of long arc story of sepsis and kind of where we are today. So recommend checking that out when it comes available this summer.
01:11:17
Speaker
Excellent. Well, want to thank both of you for all the work on the um the guidelines, but also for being so generous with your time and with your knowledge. I definitely enjoyed the conversation and learned a lot.
01:11:30
Speaker
Yeah, thanks so much for having us. Thanks, Sergio. Thank you for listening to Critical Matters, a sound podcast. Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
01:11:45
Speaker
Sound's transforming the way critical care is provided in hospitals across the country. To learn more, visit www.soundphysicians.com.