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Surviving Sepsis Campaign Guidelines 2021
12 Plays4 years ago
In this episode of Critical Matters, we will discuss the Surviving Sepsis Campaign Guidelines 2021 update.
Our guest is Dr. Laura Evans. Dr. Evans is the medical director for critical care and professor in the division of pulmonary, critical care and sleep medicine at the University of Washington Medical Center. She is the current Surviving Sepsis Campaign guidelines co-chair and the lead author for the 2021 Surviving Sepsis Campaign Guidelines.
Additional Resources:
Surviving Sepsis Campaign Guidelines 2021: https://journals.lww.com/ccmjournal/Fulltext/2021/11000/Surviving_SepExecutive Summary: Surviving Sepsis Campaign Guidelines 2021: https://journals.lww.com/ccmjournal/Fulltext/2021/11000/Executive_Summary__Surviving_Sepsis_Campaign_.14.aspx
Society of Critical Care Medicine Resources for SSC: https://www.sccm.org/SurvivingSepsisCampaign/Home
Hanlon's Razor: https://thedecisionlab.com/reference-guide/philosophy/hanlons-razor/
Books Mentioned in this Episode: Good Night Stories for Rebel Girls: 100 Tales of Extraordinary Women by Elena Favilli and Francesca Vallo: https://www.amazon.com/Good-Night-Stories-Rebel-Girls/dp/0997895810/ref=sr_1_1?crid=13KK590LSPF64&keywords=good+night+stories+for+rebel+girls&qid=1638473265&sprefix=good+night+%2Caps%2C182&sr=8-1
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Transcript
Introduction to Critical Matters Podcast
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.
00:00:14
Speaker
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.
00:00:26
Speaker
And now your host, Dr. Sergio Zanotti.
Focus on Severe Sepsis and Septic Shock
00:00:32
Speaker
In today's episode of the podcast, we will discuss severe sepsis and septic shock, a major cause of mortality, morbidity in hospitalized patients around the world.
00:00:41
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Sepsis is a complex syndrome with an important impact on our critically ill patients and healthcare system.
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For over a decade, the Surviving Sepsis Campaign has brought together representatives from various professional societies with the goal of reducing mortality and sepsis worldwide.
Guest Introduction: Dr. Laura Evans
00:00:57
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Today, we will discuss the fourth update of the Surviving Sepsis Campaign guidelines
00:01:01
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for the management of severe sepsis and septic shock in adult patients.
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Our guest is Dr. Laura Evans.
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Dr. Evans is the medical director for critical care and a professor in the division of pulmonary critical care and sleep medicine at the University of Washington Medical Center in Seattle.
00:01:18
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She joined the steering committee of the Surviving Sepsis Campaign in 2012 and is the current Surviving Sepsis Campaign guidelines co-chair.
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She's also the lead author of the 2021 guidelines that we will be discussing today.
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In addition,
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Dr. Evans is an author in the Surviving Sepsis Campaign's COVID-19 Guidelines and serves on the NIH COVID-19 Treatment Guidelines
2021 Guidelines Update Process
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Panel.
00:01:40
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Laura, welcome to Critical Matters.
00:01:43
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Thanks so much for having me.
00:01:44
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It's great to be here.
00:01:46
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Excellent.
00:01:47
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And I think as an introduction, maybe we could start with just a general overview of the general approach to these 2021 Surviving Sepsis Campaign Guidelines.
00:01:59
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Yeah.
00:02:00
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As you said in your opening remarks, the Surviving Sepsis Campaign has been around for almost 20 years now.
00:02:08
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And it started back in 2002 with kind of just a declaration of the intention to work together on an international basis to reduce mortality from sepsis and septic shock.
00:02:19
Speaker
And part of that process was the development of evidence-based guidelines.
00:02:22
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And so this is the fourth iteration or fourth revision of those guidelines.
00:02:27
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And it's on about an every four-year cycle now.
00:02:30
Speaker
Maybe we'll talk a little bit more about why it takes so long, because you often get questions about, like, what are the new guidelines coming out, and how can they take so long to come out?
00:02:38
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So this one is actually about five years after the last one, the pandemic added a little bit of time to our revision cycle, as you can imagine, from that.
00:02:46
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But I think the process of developing the guidelines has gotten more rigorous and more robust, and
00:02:55
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and even just a really clear structured process as we go through this.
00:03:01
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And that's probably not only applies to the Surviving Sepsis Campaign guidelines, but to guideline development on a larger scope from that.
00:03:10
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So the general approach of it is we start with co-chairs and co-vice chairs who are nominated by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, who are the two joint sponsoring societies.
00:03:26
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What that means is that financially the guidelines effort is supported by ESICM and SCCM.
00:03:31
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So there's no industry funding for this.
00:03:33
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There's no external sources
Public Involvement in Guidelines Development
00:03:34
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of funding.
00:03:34
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This is actually funded directly by the professional societies from that.
00:03:39
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Then as co-chairs and co-vice chairs, we start to assemble the panel of who will be participating in this guidelines process.
00:03:47
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And we have kind of two or three really sort of different categories that we work with.
00:03:52
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And one is
00:03:53
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We invite representatives from a multitude of professional societies who are stakeholders in the process of sepsis care.
00:04:02
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And that's other intensive care societies, pulmonary professional societies, nursing critical care societies, infectious disease, surgical societies, you name it, from across the world from that.
00:04:13
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So we end up with about 25 appointees from societies that have been invited to be participants in the process from that.
00:04:22
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We also then have
00:04:24
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at large members that we can appoint to the guidelines panel.
00:04:28
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And we use those spots to make sure that we have a diverse and hopefully more, we have pretty representative guidelines panel from that.
00:04:37
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So we want people from different professional backgrounds, right?
00:04:40
Speaker
We want nurses, we want clinical pharmacists, we want intensivists, we want emergency medicine physicians, you name it.
00:04:48
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And we want people from around the world
00:04:50
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And from pertinently, I think obviously people of different genders, but also people who represent different economic circumstances.
00:04:59
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So in this revision, we have more representation internationally and we have more representation from low and middle income countries than we had previously, which we think is really important in terms of moving the guidelines forward and making it a truly international document and international tool.
00:05:17
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because clearly the global burden of sepsis is also very much weighted towards the low and middle income settings, much more so than high income settings, as big of a problem as it is here in the United States and in Western Europe from that.
00:05:30
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So that's kind of how we start with the panel.
00:05:32
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And then one piece that I really wanna highlight that was a little bit different this time around is we also invited six public members or public representatives to the process this time
00:05:44
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Previously, we had had a public or a lay person representative to the process, but it was really just one person from that.
00:05:51
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And here we thought that that was not a sufficient input of patient and family perspective.
00:05:56
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So this time we had six public representatives and they were either former ICU patients or former patients who had survived sepsis or family members of persons who had had sepsis and survived or had sepsis and died.
00:06:10
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And they were a really critical piece of the guidelines panel in terms of helping contextualize everything that we were looking at and saying, well, what does this matter to patients?
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How does this impact the patients at the end of the day?
00:06:25
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Because that's fundamentally why we're doing this.
00:06:28
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So I was really glad that we have such robust public representation on this guidelines panel.
00:06:33
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So that's kind of how we start with the panel from that.
00:06:35
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Do you want me to go through kind of the process of how we
00:06:39
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kind of go through guidelines development or what's helpful to you next?
00:06:43
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Well, I think that first just want to mention and emphasize what you said about having patient representation or family representation, right?
00:06:50
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We keep talking about being patient-centered and what we do, yet we develop so many things in medicine in isolation of ultimately who we're trying to benefit.
Understanding GRADE Methodology
00:07:01
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So I think that's a big plus.
00:07:02
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And I have seen an increase in committees and other guidelines of really trying to bring to the table
00:07:09
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those stakeholders that at the end of the day are the recipients of all our efforts.
00:07:12
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So I think that's to be applauded.
00:07:14
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I think that maybe to move on, we can definitely, we'll link all the guidelines and the executive summary in the show notes and people can go there for more details.
00:07:24
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But I do believe that perhaps an overview of the type of recommendations, we have strong versus weak, we have best practice and the strengths of evidence in terms of how that plays into the
00:07:36
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the recommendations for clinicians would be valuable.
00:07:40
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Yeah, thanks for that.
00:07:42
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Yeah, so we follow grade methodology, which, as I mentioned before, is very structured and rigorous in terms of how we formulate and define recommendations.
00:07:53
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And so there are different categories of recommendations, like you were just alluding to.
00:07:57
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There's strong recommendations, there's weak recommendations, and you can
00:08:02
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you can tell what's a strong recommendation or a weak recommendation just by how it's phrased within the text.
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So if it's a strong recommendation, we use the words we recommend, followed by whatever intervention we're referencing there.
00:08:16
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If it's a weak recommendation, we use the phrase we suggest.
00:08:20
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So again, so that difference between we recommend says this is a strong recommendation, we suggest means that it's a weak recommendation.
00:08:28
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Each strength of recommendation is then followed by a rating of the quality of evidence, and that can be anywhere from high quality to very low quality of evidence.
00:08:38
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And so we use the GRADE methodology again to go through and we look at several different factors when we're rating the quality of the evidence behind a recommendation.
00:08:48
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And that may be, you know, are these well, do we start with well-designed randomized controlled trials?
00:08:53
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Do we start with observational studies?
00:08:55
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And those give us sort of a benchmark of where to start.
00:08:57
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And then evidence can be upgraded or downgraded based on several different factors.
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Is there a consistency of effect seen across multiple studies?
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Do the studies that are informing the recommendation directly apply to this patient population?
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Or are they extrapolated from sort of larger patient populations of severely ill or acutely ill patients?
00:09:19
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So we can use
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categories like indirectness and inconsistency to downgrade evidence or upgrade evidence if those factors are not present.
00:09:29
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We also obviously look at things like risk of bias in the ratings of these studies to help us grade the quality of evidence.
00:09:34
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So each recommendation will have a string and then a quality of evidence statement around it, which represents sort of our certainty around that statement.
00:09:44
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And like you were saying,
00:09:46
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whether a recommendation is weak or strong, has implications for how we think about implementation of that recommendation.
00:09:54
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It may have implications for patients.
00:09:56
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It has implications for clinicians, and it probably has implications for policymakers as well.
00:10:01
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So if you think about a strong recommendation from a patient perspective, functionally what we're saying is most individuals or most patients would want the recommended treatment or intervention, that only a small proportion probably would not want that.
00:10:15
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Whereas a weak recommendation, right, a suggestion, the sort of patient implication of that is, you know, that we think the majority of patients in that situation would want the suggested course of action or suggested intervention, but many probably would not.
00:10:30
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And so it really is an area for contextualization and obviously incorporation of patient values and preferences and other factors that might impact your decisions about whether to pursue that intervention.
00:10:43
Speaker
Similarly, from a clinician standpoint, a strong recommendation means we should do that most of the time, right?
00:10:50
Speaker
And we should have a reason, obviously, to deviate from doing that if we're going to not do it.
00:10:57
Speaker
Whereas a weak recommendation means probably different choices might be appropriate in different circumstances for different patients.
00:11:02
Speaker
So I kind of think of it sort of as almost as something to take under consideration, but really to apply within the clinical context as well.
00:11:12
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And then from a policy standpoint, most of the time we're thinking about strong recommendations as potentially things that can be adapted for policy level things or performance indicators, dashboards, things like that.
00:11:24
Speaker
And weaker recommendations or suggestions probably have sort of variable policy implications where if you're saying that we're not recommending this treatment strongly, is it really something that you want to put on your local performance dashboard when you're saying that variability and implementation and context-specific considerations might
00:11:42
Speaker
impact whether you think you should do that treatment or not.
00:11:45
Speaker
So again, this is all within the GRADE framework.
00:11:48
Speaker
There's really great resources out there.
00:11:50
Speaker
If there's any like sort of burgeoning guidelines nerds out there, there's some really great tools.
00:11:55
Speaker
If you go to the GRADE website and kind of look through this and there's a bunch of online trainings and things like that.
00:12:02
Speaker
But I think it's important to know the distinction between strong and weak recommendations because they're not all, they don't all carry the same weight and the same implications.
Sepsis Guidelines vs. Bundles
00:12:12
Speaker
And for those who really like numbers, would it be fair to say that a strong recommendation is maybe a 90% of patients would want it or 90% of clinicians or clinical situations would require it and perhaps a week is 60%?
00:12:26
Speaker
Like you said, it's a majority, but there's still enough room that there might be some debate.
00:12:32
Speaker
Yeah, I mean, we haven't traditionally put numbers on it, but I think somewhere in that ballpark, yeah, where it's sort of, you're talking about a preponderance, right, in a strong recommendation versus a
00:12:41
Speaker
you know, most.
00:12:42
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So, you know, if that's 90, 60, that probably sort of feels about right.
00:12:45
Speaker
Although traditionally we don't truly put numbers on it per se.
00:12:50
Speaker
Excellent.
00:12:51
Speaker
Laura, I wanted to ask you also about the best practice statements.
00:12:54
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Could you just give us a synthesis of what does the committee or the guidelines mean when they say this is a best practice statement?
00:13:02
Speaker
Yeah, thanks for that.
00:13:03
Speaker
So a best practice statement is essentially a strong recommendation
00:13:09
Speaker
that is an ungraded statement.
00:13:11
Speaker
And so it has to meet kind of certain criteria.
00:13:16
Speaker
And the idea is it's, some people use the phrase of it's kind of like a mom and apple pie statement, right?
00:13:22
Speaker
Where it's sort of, where everybody says this is a really strong recommendation, but conducting the study is really not feasible to do that.
00:13:33
Speaker
So one example I would say, and it happens to be like
00:13:37
Speaker
My personal favorite statement from the 2016 guidelines is this, that sepsis and septic shock are medical emergencies and treatment and resuscitation should begin immediately.
00:13:50
Speaker
So that's a best practice statement, right?
00:13:51
Speaker
It's a strong recommendation, but it's ungraded or ungradable, perhaps better said.
00:13:56
Speaker
So what it means is you can't really design the study to say, I'm going to randomize to treating sepsis like a medical emergency versus not from that.
00:14:07
Speaker
where we think the benefits are overwhelming compared to the possible downsides of it.
00:14:15
Speaker
So there, again, in grade methodology, there are distinct criterias that need to be applied in order for something to constitute a best practice statement.
00:14:24
Speaker
If something can be clearly studied and we just don't have the evidence base
00:14:31
Speaker
applying a best practice statement would not be appropriate in that setting.
00:14:34
Speaker
In that sense, we should actually grade it and say, we're going to issue a strong or weak recommendation and have that quality of evidence statement behind it as well.
00:14:43
Speaker
And that might be low or very low at that time.
00:14:46
Speaker
So we do have best practice statements around it.
00:14:48
Speaker
And I, again, probably sort of come back to this phrasing of these are sort of just general, like good practice,
00:14:54
Speaker
mom and apple pie, but sometimes they need to be stated just to keep us grounded and contextualized from that.
00:15:02
Speaker
So that's where we use best practice statements.
00:15:03
Speaker
We also introduced something in this revision of the guidelines, which is an in-hour practice statement, which obviously sounds a little bit similar to a best practice statement, but it sort of represents a statement of where the panel comes down in terms of current practice.
00:15:23
Speaker
And so it's not
00:15:24
Speaker
a graded recommendation.
00:15:26
Speaker
It's not, you know, from a systematic review of the literature.
00:15:32
Speaker
But for example, when you look at the recommendation in the 2021 revision with, that comes around the addition of vasopressin to norepinephrine, right, when you need a second agent vasopressor from that.
00:15:44
Speaker
And then we have an in our practice statement and in the remarks session that's there, which says, basically provides additional guidance as to at what threshold of
00:15:54
Speaker
norepinephrine dosing, do panel members tend to add vasopressin from that.
00:15:59
Speaker
And so it's just to provide a little bit more concrete, specific guidance, but it's not a graded recommendation and is not something that is based purely on what's out there in the literature.
00:16:14
Speaker
It really is a reflection of what the current practice is of the members of the guideline panel.
00:16:20
Speaker
Excellent.
00:16:21
Speaker
Before we dive into the actual recommendations or some of the clinical guidelines recommendations, I just want to address the overall best use of the guidelines.
00:16:35
Speaker
We were talking before we started recording that obviously the Surviving Sepsis Campaign and its guidelines have had a tremendous impact over almost 20 years in terms of really shaping and changing the way we talk about sepsis.
00:16:48
Speaker
But as a comprehensive and such a large body
00:16:51
Speaker
of work, it has obviously a lot of followers and adopters, but there's also a lot of detractors and people who have focused on aspects that may be out of control of the guidelines in terms of lack of evidence or disagree with certain recommendations from the past.
Initial Resuscitation Strategies
00:17:07
Speaker
But ultimately, I think that it's important for us to understand what the guidelines are and what they're not and how do you see it's best utilized by our audience, which are usually clinicians at the bedside.
00:17:21
Speaker
Yeah, thanks.
00:17:21
Speaker
I think that's a great question from that.
00:17:23
Speaker
And I think, you know, the SSC, you know, has been, I think, enormously successful overall in terms of just raising the bar of conversations around sepsis and raising people's awareness to the importance of, you know, timely and appropriate sepsis care from that.
00:17:45
Speaker
And
00:17:47
Speaker
But it is a process in evolution also.
00:17:50
Speaker
And as you said, it has generated controversy throughout its history from that.
00:17:56
Speaker
And I think, you know, I think there are different elements of the surviving sepsis campaigns.
00:18:01
Speaker
One I think that's probably worth talking about directly is, you know, the relationship between guidelines and bundles.
00:18:10
Speaker
from that, because I think oftentimes we kind of get them all sort of mixed up and conflated in our heads about that guidelines and bundles are kind of the same thing and that they're all, and they're related clearly.
00:18:25
Speaker
But the guidelines development process, and so this whole multi-year process that we go through in terms of getting this big panel together, generating KIKO questions, doing the systematic reviews,
00:18:40
Speaker
generating and voting on recommendations, drafting these guidelines, the multiple levels of peer review, that's all the guideline development process from that.
00:18:49
Speaker
And that's actually a separate process from the development and derivation of these bundles or implementation bundles from that.
00:18:58
Speaker
The idea is, I think, as you said during the intro, we ended up producing a guidelines document that has 93 recommendation statements in it, right?
00:19:06
Speaker
Which is a huge volume of work,
00:19:09
Speaker
And for that person at the bedside going, okay, what do I do with the patient in front of me?
00:19:13
Speaker
93 recommendations is like fundamentally pretty impractical to go, oh yeah, I can implement that tomorrow, right?
00:19:20
Speaker
So the bundles are developed through a different process than the guidelines.
00:19:27
Speaker
And they're meant to kind of, you know, sort of distill down some of the most essential elements into pieces that you can sort of readily apply at the bedside
00:19:37
Speaker
and track your performance around, right, from that.
00:19:41
Speaker
And then those bundles have led to
Dynamic Measures in Fluid Resuscitation
00:19:45
Speaker
adoption by the National Quality Forum of the Sepsis 0500 measure, which then was adopted and modified by CMS as SEP1.
00:19:54
Speaker
So while these processes are all related, they're not actually interchangeable.
00:19:58
Speaker
And I think that's where, quite honestly, I think that's where some of the controversy around the guidelines has developed is from sort of this,
00:20:07
Speaker
even misconception that they're all sort of directly related, they're all the sort of direct same process from that.
00:20:14
Speaker
So to get back to your question of what should we do with these guidelines as clinicians, I think I would use them in a couple of different ways.
00:20:21
Speaker
One is, yes, as a sort of framing process to approach care of patients with sepsis and septic shock.
00:20:29
Speaker
There are always reasons that you should potentially deviate from a clinical protocol.
00:20:34
Speaker
I think, you know, one of the,
00:20:37
Speaker
arts of medicine is knowing when the protocol doesn't apply, right?
00:20:42
Speaker
So I think guidelines are a great sort of framing document reference of like, what should I usually do?
00:20:50
Speaker
And then we all have to obviously be aware of when we should, when the guidelines potentially don't apply and when I should do something different or deviate from them.
00:20:59
Speaker
I think the other piece around the guidelines that I often I think is overlooked is to serve as
00:21:06
Speaker
kind of a snapshot status report of where are the evidence gaps, where are the research gaps in terms of treating the clinical syndrome of sepsis from that.
00:21:17
Speaker
Things have changed and evolved over your career and over my career, right?
00:21:21
Speaker
We've seen how we approach sepsis vary quite a bit from that.
00:21:26
Speaker
And so I look at the guidelines and I look at the recommendation statements, I look at the quality of evidence, I look at the statements where
00:21:33
Speaker
you know, despite asking the PICO question and doing the literature review and really, you know, putting 60 smart people in a room to hash it out, where we can't come up with a recommendation because the evidence just isn't there.
00:21:46
Speaker
So I think about it also as sort of a status report on where we are as a field and what we need to do in terms of a research agenda to help move the entire field and move patient care forward.
00:21:57
Speaker
So I kind of look at those two things as a framework for how we approach patient care and then this sort of
00:22:02
Speaker
I don't want to say a roadmap because it's not explicitly designed for that purpose, but a method to highlight a potential research agenda.
00:22:14
Speaker
Excellent.
00:22:14
Speaker
So let's dive into some of the actual recommendations and some of the important clinical items that we should be thinking about when we treat patients with severe sepsis and septic shock.
00:22:25
Speaker
And obviously, Laura, as we mentioned, this is a very comprehensive document with over 93 recommendations.
00:22:32
Speaker
we are gonna pick and choose some of the ones that I think are either.
00:22:36
Speaker
Yeah, we'll lose everybody if we try to do it all.
00:22:38
Speaker
Yeah, pick and choose some of the ones that are more subtle changes or that have maybe perhaps a greater impact on the immediate care.
00:22:47
Speaker
And then again, obviously refer everybody to the guidelines themselves and their executive summary to get more information.
Antibiotic Timing and Severity Considerations
00:22:54
Speaker
So why don't we start with screening initial resuscitation and
00:22:59
Speaker
One of the, I would say, one of the most discussed items is the initial fluid bolus and the famous 30 mLs per kg.
00:23:08
Speaker
Could you just tell us where we stand today in 2021 and what was the thought process behind that?
00:23:13
Speaker
Sure.
00:23:14
Speaker
So that one really hasn't changed a great deal.
00:23:17
Speaker
When you read the phrasing of the recommendation, what we're saying is, and I'm quoting from the guidelines themselves right now, is it says, for patients with sepsis-induced hypoperfusion or septic shock, we suggest...
00:23:29
Speaker
that at least 30 milliliters per kilogram of IV crystalloid be given within the first three hours of resuscitation.
00:23:35
Speaker
And in the 2021 revision, that's a weak recommendation based on low quality of evidence.
00:23:40
Speaker
So that is a downgrade in the strength of recommendation from the 2016 revision where we had a strong recommendation based on low quality evidence.
00:23:48
Speaker
Now we have a suggestion or a weak recommendation based on low quality of evidence for 30 mils per liter of initial fluid bolus.
00:23:56
Speaker
And to arrive at this, we looked at what the available literature was out there from that, from the patient-level meta-analysis of the large multi-center randomized controlled trials of process promise and ARISE to the observational work from a multitude of sources around implementation of sepsis bundles, including the New York State
00:24:19
Speaker
statewide sepsis performance initiative that was published in the, that part of it published in the Blue Journal that showed an association of a reduction in mortality when patients who were hypotensive or had elevated lactates received 30 mils per kilo of fluid upfront compared to those who did not.
00:24:36
Speaker
So there's a good volume of observational data, and then we're looking at the sort of control arm mortality as well as the treatment arm mortality in the patient-level meta-analysis from these large multicenter RCTs of early goal-directed therapy.
00:24:50
Speaker
all of which sort of had an average of about 30 mils per kilo for fluid administered prior to randomization in
Fluid Choices and Vasopressor Use
00:24:58
Speaker
those studies.
00:24:58
Speaker
So both the sort of idea that 30 mils per kilo is common practice, as well as in multiple observational studies, including several thousand patients, or in the New York State database, up to 50,000 emergency department patients, is associated with a reduction in mortality.
00:25:15
Speaker
But there is no RCT data of
00:25:19
Speaker
randomizing patients to 30 mils per kilo compared to randomizing them to 15 mils per kilo or 20, whatever, pick the number from that.
00:25:27
Speaker
So that's how we end up with low quality of evidence.
00:25:30
Speaker
And after a lot of discussion and banter back and forth amongst the guidelines panel, we concluded that we should downgrade the strength of the recommendation from strong to weak from that.
00:25:43
Speaker
So that's where we landed with 30 mils per kilo.
00:25:45
Speaker
I think critically what we want to, and another piece that I'd like to emphasize is that we're taught this particular
00:25:56
Speaker
question is focused really just on that initial fluid resuscitation volume.
00:26:02
Speaker
We asked a different question about what to do with subsequent resuscitation, right, liberal versus restrictive fluid strategies from that.
00:26:10
Speaker
And we didn't find any, in any of the literature that we looked at, we didn't find any convincing evidence of patient harm associated with the 30 mLs per kilo up front.
00:26:19
Speaker
Yeah.
00:26:20
Speaker
And I think another important aspect of the 30 mLs per kilo is that
00:26:25
Speaker
it's really for patients who have hypoperfusion or septic shock.
00:26:29
Speaker
It doesn't mean that you give it to everybody who you think has an infection.
00:26:33
Speaker
And that has been, I think, a problem in clinical practice.
00:26:38
Speaker
And the other point that is often brought up is what about patients with heart failure and renal failure?
00:26:47
Speaker
And again, my understanding, maybe you can dig a little deeper here, is that
00:26:52
Speaker
the literature doesn't really support that we're harming patients when they need the fluids, whether they have a diagnosis of heart failure or renal failure.
00:27:00
Speaker
But ultimately, like you said, it's a guideline and you have to evaluate each patient individually.
00:27:05
Speaker
Yeah, I think all of those things are true.
00:27:07
Speaker
And I strongly support that if you're assessing a patient at the bedside and you think that they are in active decompensated heart failure and acutely volume overloaded,
00:27:18
Speaker
you should use your clinical judgment and then document it, right?
00:27:22
Speaker
I think we're all trained professionals and we should use our professional training to make our best judgments at the bedside as well.
00:27:32
Speaker
But yeah, when you look at these observational studies that include patients with a history of heart failure or a history of chronic kidney disease, there's certainly no suggestion that patients with heart failure or kidney disease
00:27:46
Speaker
respond differently or respond adversely to that initial 30 mils per kilo bolus from that.
00:27:52
Speaker
And we saw that in the New York State data.
00:27:54
Speaker
And then I think the other study that's really nicely done around that comes out of the, from Vinnie Lou's group from Kaiser Permanente in Northern California, where they looked at actually, you know, a little bit of an expanded indication for fluids, because they implemented a sepsis bundle that included the 30 mils per kilo fluid resuscitation
00:28:13
Speaker
for patients who were not hypotensive and had sort of intermediate lactate values.
00:28:18
Speaker
So this was a lactates two to four millimoles per liter and were not hypotensive.
00:28:24
Speaker
And they implemented a sepsis bundle that included fluid resuscitation for those patients.
00:28:28
Speaker
So even a little bit expanded from the guidelines recommendation in terms of the population receiving fluids there.
00:28:34
Speaker
And when they looked at the signal around implementation of this bundle,
00:28:40
Speaker
in patients with heart failure and kidney failure, they actually had the largest signal of mortality benefit from implementation of this bundle compared to all comers.
00:28:48
Speaker
So certainly we don't see in the existing literature, we don't see suggestions of harm measured on any kind of population basis or, you know, that we can see reported in these observational studies.
00:29:01
Speaker
Does that mean definitionally that, you know, nobody, none of us have ever fluid overloaded a patient?
00:29:07
Speaker
by giving the 30 mils per kilo?
00:29:08
Speaker
Of course not, right?
00:29:09
Speaker
I mean, that's the difference between the guidelines and really making that astute clinical judgment at the
Corticosteroids and Vitamin C in Septic Shock
00:29:17
Speaker
bedside from that.
00:29:17
Speaker
But again, I would kind of use the framing as like, that's my starting point
00:29:23
Speaker
And I'm going to look if there's a reason why I think it's acutely contraindicated, but it's going to be kind of my go-to maneuver for about patients who are hypotensive or hypoperfused as evidenced by an elevated lactate, unless there's some reason that I think I'm going to actually push them into acute decompositive heart failure, for example.
00:29:44
Speaker
Perfect.
00:29:45
Speaker
And in terms of guidance of that initial resuscitation, could you just make some comments specifically on
00:29:51
Speaker
the recommendations on dynamic versus static parameters, lactate levels, and the new recommendation in capillary refill?
00:30:01
Speaker
Yeah, so the capillary refill one, I think, is definitely a new one.
00:30:04
Speaker
I think it's one I particularly like because I think, again, we're talking about trying to
00:30:12
Speaker
provide useful guidance that can be applicable in a multitude of settings, right?
00:30:17
Speaker
And so for those, you know, we all work in different settings.
00:30:20
Speaker
Some of us work in, you know, really well-resourced environments.
00:30:23
Speaker
Some of us work in less well-resourced environments.
00:30:26
Speaker
Some people, you know, emergency departments are particularly busy and overwhelmed, although maybe in the days of COVID that's more the norm rather than the exception.
00:30:37
Speaker
And we all have different access to, whether it be different commercial equipment to help us measure fluid responsiveness or not any access to it as well.
00:30:47
Speaker
So I really like the concept of capillary refill as a readily available non-technology-based tool to help us assess our adequacy of resuscitation for that.
00:31:02
Speaker
So that's our recommendation around the use of capillary refill as an adjunct.
00:31:07
Speaker
to other markers of assessing our resuscitations is really based on the Andromeda shock trial, which showed obviously non-inferiority of the cap refill approach compared to using lactate clearance from that.
00:31:21
Speaker
So I think that I'm really happy that that got included in there, because I think we often kind of anchor on technology fixes to things and lose that kind of instinct to go back to the bedside and say, okay, how does my patient actually,
00:31:36
Speaker
And what are they actually doing?
00:31:38
Speaker
And so I think cap refill is a nice tool for that.
00:31:42
Speaker
We have a suggestion that's pretty much unchanged from 2016 about using dynamic rather than static parameters to help guide resuscitation, particularly after that initial 30 mils per kilo from that.
00:31:54
Speaker
One question that often gets answered is, okay, well, what do you mean, like, which dynamic measure should I use from that?
00:32:01
Speaker
And, you know, our assessment of the state of the evidence at this point was that
00:32:06
Speaker
there really isn't a sufficiently strong evidence base to recommend one dynamic measure over a different dynamic measure to help with that assessment of fluid responsiveness after initial resuscitation.
00:32:19
Speaker
So, you know, my advice would be use what you have or, you know, use what you're comfortable with and have readily available to you to help you guide that using your dynamic measures of whether it be
00:32:33
Speaker
passive leg raise and pulse pressure variation or ECHO for those who are skilled in its use and applicability at the bedside from that.
00:32:42
Speaker
But I think the key take-home point was just these static measures are probably inferior to using dynamic measures, but we don't know exactly what dynamic measure outperforms other dynamic measures at this point in time.
00:32:57
Speaker
And any comments on lactate?
00:32:59
Speaker
Oh yeah, lactate.
00:33:02
Speaker
So I think lactate was an interesting one because there's multiple, you know, potential uses of lactate and sepsis, right?
00:33:09
Speaker
There's lactate as a prognostic marker, right, where elevated lactates are associated with worse outcomes for patients.
00:33:17
Speaker
There's, you know, I think good, reasonably good data about lactate clearance as a target for resuscitation from that
00:33:25
Speaker
And then we now have obviously the revised 2016 sepsis definitions that include an elevated lactate within the definition of septic shock from that.
00:33:36
Speaker
So I do think that there's a role for using lactate clearance as a marker of my resuscitation and using that as one factor amongst many to help me guide resuscitation for patients with septic shock from that.
00:33:54
Speaker
The, you know, in terms of the diagnostic piece for, you know, is the septic shock present by the 2016 definition or not, you kind of have to measure the lactate in order to answer that.
00:34:08
Speaker
That, you know, I know we're off topic with the definitions here.
00:34:12
Speaker
That, for me, raised an issue with the definition in the first place because in many parts of the world where, you know, lactate measurement may not be readily available,
00:34:22
Speaker
Does that mean I can no longer even make a diagnosis of septic shock if I can't measure a lactate?
00:34:28
Speaker
But that's obviously not the topic of discussion today, but I think it's an interesting consideration overall.
00:34:38
Speaker
Let's move on and talk about infection.
00:34:41
Speaker
And Laura, I think that initiation of antibiotics obviously is a huge topic of discussion.
00:34:48
Speaker
I want to believe that most people would agree that if you're super sick, earlier is better.
00:34:53
Speaker
But in terms of how to define that, I think has caused some consternation and some debate.
Long-term Outcomes and Research in Sepsis Management
00:34:59
Speaker
And this is also something that I think the new guidelines have tried to capture based on the available evidence in a different way.
00:35:05
Speaker
And that's expressed in that figure one in the manuscript, which I recommend everybody take a look.
00:35:10
Speaker
But maybe you could tell us a little bit of where we stand there today.
00:35:14
Speaker
Yeah.
00:35:17
Speaker
I think you're right, and I hope you're right in the sense that I think for patients with sepsis and septic shock, I think there's probably fairly little debate at this moment in time that timely initiation of antimicrobial therapy is a major driver of patient outcome.
00:35:37
Speaker
And where we have ended up, I think, having more vigorous debate over the last several years is in the population that's
00:35:47
Speaker
you know, not clearly septic, and how does that relate to, you know, our concerns about antimicrobial stewardship and driving antimicrobial resistance and overuse of antimicrobials, all of which are legitimate concerns, right, and so where we approached it with this guideline is in, I think, figure one, as you said, sort of
00:36:11
Speaker
I think hopefully the community will tell us, right?
00:36:14
Speaker
But hopefully provides a useful tool for the adaptation of that.
00:36:20
Speaker
And I think thinking about it as, I think it's probably the way we fundamentally approach patients at the bedside, which is both looking at how sick my patient is.
00:36:34
Speaker
So in that sense, we're categorizing recommendations as in shock or not in shock.
00:36:41
Speaker
And then how likely do I believe an infection is?
00:36:45
Speaker
So I kind of think about those as like an X axis and a Y axis.
00:36:50
Speaker
So how sick is my patient and how likely is infection?
00:36:54
Speaker
And so if I'm dealing with a patient that's sicker, i.e.
00:36:57
Speaker
a patient in shock, I need less certainty on the infection access to feel like I should give antimicrobial therapy upfront
00:37:08
Speaker
because my window of error, if, you know, my margin of error or window of missed opportunity, if it turns out that that patient has infection and they're already in shock, is so small.
00:37:18
Speaker
So then I sort of get that first dose in, you know, let the dust settle, see what's going on, and then hope, you know, if they're not infected, you know, discontinuity antibiotics.
00:37:28
Speaker
So more sick, you know,
00:37:31
Speaker
likely infection to even less certainty of infection than I think we're targeting getting those antibiotics in immediately, ideally within an hour.
00:37:40
Speaker
Whereas if you're in the less sick kind of axis, right, where you're not in shock and you have less certainty that an infection is causing whatever the acute illness presentation is, then perhaps you have a little bit more time to do a focused evaluation to
00:38:00
Speaker
you know, get some initial labs back, you know, get another x-ray, get a UA, and move yourself either further along towards more certain that there's an infection or less certain that there's infection.
00:38:14
Speaker
So using that time then for this focused evaluation to determine whether an infection is present or not, and for that population, so not in shock,
00:38:22
Speaker
and less certain of infection.
00:38:25
Speaker
We're saying, really do this focused evaluation, and then if you think there's infection, get those antimicrobials started within three hours.
00:38:32
Speaker
So it's still the one hour, three hour framework, but it now sort of explicitly incorporates both of these concepts of how sick is my patient and how certain am I that there's an infection present.
00:38:44
Speaker
Does that make sense?
00:38:48
Speaker
It does, and I think also it's important to emphasize that
00:38:52
Speaker
This is another area that is hard to study with randomized controlled trials and that the data that we have is mixed, it's retrospective.
00:39:01
Speaker
But again, it points to what you're saying, that in patients who are sicker, it's easier to show that there's a time sensitive component and that really delays an antibiotic, appropriate antibiotics have an impact on mortality.
00:39:16
Speaker
And perhaps in patients that are not as sick, it's a bit harder to show that.
00:39:20
Speaker
So I do believe that
00:39:21
Speaker
having that clinical distinction between how sick is my patient first and how certain am I that this is an infection second should also guide us and try to help us make this better.
00:39:32
Speaker
And the way I always phrase it to my colleagues is if I am lying in an ED with septic shock, I would rather have appropriate antibiotics sooner rather than later.
00:39:43
Speaker
You and me both.
00:39:47
Speaker
Absolutely.
00:39:49
Speaker
So moving on to hemodynamics, choice of fluid, this is something that we've been debating for some time now and has resulted in some RCTs, but more importantly for our discussion today, it also has resulted in maybe a change in the recommendation.
00:40:10
Speaker
Yeah, we'll talk about it.
00:40:13
Speaker
Although unfortunately, our literature review date for the guidelines closed before the release of one of the newest studies, the BASICS trial coming out of Brazil.
00:40:23
Speaker
So the recommendation actually does not reflect the data from BASICS from that.
00:40:29
Speaker
So we do issue a weak recommendation based on low quality of evidence favoring the use or suggesting the use of balanced crystalloids instead of normal saline for resuscitation for that
00:40:40
Speaker
And we looked at a multitude of outcomes to try to arrive at that recommendation, including mortality, new onset kidney dysfunction, and found some signal that of favorable outcomes for balanced crystallites compared to normal salines.
00:40:57
Speaker
The BASICS trial, most people will know, did not show a difference between the use of normal saline and balanced crystalloid.
00:41:05
Speaker
when it's time to relook at this recommendation as well, that'll get included and it may or may not influence the directionality of this current suggestion for balanced crystallites compared to normal saline for resuscitation from that.
00:41:19
Speaker
So I think it does raise this point of, at some point we have to cut off, there's always new data coming out, right?
00:41:25
Speaker
And at some point we have to sort of just cut off the additional data going into the guidelines and then they don't come out the very next day, right?
00:41:32
Speaker
They still have to go through the
00:41:34
Speaker
writing process and the peer review process and the publication process.
00:41:37
Speaker
So there's a little bit of a built-in delay with that.
00:41:41
Speaker
And so, you know, there's work going on to think about how do we, you know, update the guidelines on an interval basis if we need to, if there's a really a practice-changing type of recommendation or practice-changing study that would, you know, say clearly what our recommendation is wrong.
00:41:57
Speaker
But for now, we do have a weak suggestion or weak recommendation or suggestion for balanced crystallizing over normal saline for resuscitation.
00:42:04
Speaker
And it's very interesting in terms of watching the evolution, because in the first iteration of the guidelines, the discussion really was around albumin versus crystalloids, right?
00:42:13
Speaker
Collage versus crystalloids.
00:42:15
Speaker
And that we've learned a lot, but at the end, I mean, maybe what we do at the bedside hasn't changed that much, but there's also recommendations for albumin.
00:42:23
Speaker
Could you just comment on those briefly, Laura?
00:42:26
Speaker
Yeah, the albumin one is always a problematic recommendation, though.
00:42:29
Speaker
I think you're right in that, that
00:42:32
Speaker
the amount of discussion has really kind of tamped down over time is that I think we're just using less colloid for resuscitation than we used to, that we're clearly recommending crystalloid over colloid now.
00:42:44
Speaker
But defining the population for when you might use albumin, I think is still a very tricky one from that.
00:42:51
Speaker
And so we still have a suggestion for albumin who receive, for patients who receive large volumes of crystalloids over crystalloids alone.
00:43:00
Speaker
But where we always get kind of bogged down in the discussion on the guidelines panel is what actually constitutes a large volume, right?
00:43:07
Speaker
And does that mean the same thing to you as it does to me, to somebody else from that?
00:43:13
Speaker
But where we are with the literature base really precludes our ability to say at what volume is that true, right?
00:43:23
Speaker
At what volume should we set that threshold and define it within the guidelines from that?
00:43:29
Speaker
Unfortunately, I think we end up with a little bit of a vague statement about suggesting the use of albumin in those who receive large volumes of crystalloids over crystalloids alone.
00:43:40
Speaker
And so it's sort of left to you as a clinician at the bedside to use your clinical judgment to say, I think this is a large enough volume of crystalloid that I'm going to add some albumin from that.
00:43:54
Speaker
And, you know, I think this would be a place where it would be very interesting to do in our practice statement and see how much variability there is around what threshold that is for different people.
00:44:07
Speaker
Excellent.
00:44:07
Speaker
The other cornerstone of hemodynamic support and septic shock, obviously, is the use of vasopressors.
00:44:13
Speaker
And I wanted to ask you, Laura, specifically if you could comment on choice of vasopressor and the administration of vasopressors in a timely manner
00:44:23
Speaker
which sometimes might require the use of a peripheral line.
00:44:27
Speaker
Yeah, so we continue to recommend using norepinephrine as the first line agent from that.
00:44:34
Speaker
And we did comparisons with multiple agents there, dopamine, vasopressin, surlipressin, epinephrine, and angiotensin II were the agents we compared norepinephrine to.
00:44:47
Speaker
So there's actually different quality of evidence ratings for each comparison agent from that,
00:44:53
Speaker
have a strong recommendation for norepinephrine as the first-line agent over other vasopressors.
00:45:00
Speaker
In a nod to the inclusion particularly of panelists from low and middle income countries, we also noted that norepinephrine is not available globally in every setting from that.
00:45:12
Speaker
It's not actually on the WHO list of essential medicines from that.
00:45:16
Speaker
So in some areas of the world, you can't actually use norepinephrine because it's not available from you.
00:45:23
Speaker
We then go on to suggest vasopressin instead of just escalating the dose of norepinephrine for septic shock where you're not able to achieve the adequate MAP or the MAP you're targeting from that.
00:45:37
Speaker
And that's a weak recommendation, a suggestion based on moderate quality of evidence.
00:45:42
Speaker
And this is where we include this, what, you know,
00:45:45
Speaker
this in our practice statement about where do the panelists fall on what that threshold is to consider adding vasopressin.
00:45:54
Speaker
So the range for the panelists reporting what their practice was in terms of when to start vasopressin is usually when the dose of norepinephrine was in the range of 0.25 to 0.5 mics per kilo per minute.
00:46:06
Speaker
So kind of moderate to high dose norepinephrine.
00:46:09
Speaker
was the threshold that most panelists would have used to add vasopressin as this preferential second-line agent from that.
00:46:18
Speaker
We then go on to say, if despite norepi and vasopressin, and I think this probably should also trigger a discussion of what are the goals and is continued escalation of therapy within the patient's values and preferences,
00:46:35
Speaker
But for septic shock and inadequate MAPs, despite norepi and vasopressin, we suggest adding epinephrine from that.
00:46:42
Speaker
So that's kind of the vasopressor cascade as we defined it in this one.
00:46:46
Speaker
The big difference, I think, rather than the choice of agents and selections, although last time we had sort of a add vasopressin or epinephrine statement, and now we're favoring vasopressin,
00:46:59
Speaker
as a second line agent.
00:47:00
Speaker
The big distinction, I think, is that we suggest starting vasopressors peripherally rather than delaying until a central line can be secured.
00:47:09
Speaker
And I think that's kind of a practice change.
00:47:12
Speaker
It is a suggestion.
00:47:13
Speaker
It's a weak recommendation.
00:47:15
Speaker
But I think it's potentially practice changing compared to how we used to approach vasopressor initiation in patients with septic shock, which was to get the line in first
00:47:26
Speaker
and then start the vasopressors.
00:47:28
Speaker
Whereas now we're saying, you know what, don't wait, work on getting the line, but don't wait, start the vasopressors and then get the line in.
00:47:36
Speaker
And so you don't have hopefully these prolonged periods of hypotension while you're waiting for central access, which I think we all know from our practices can take a variable amount of times, particularly, and probably depends a good bit on our different practice settings.
00:47:52
Speaker
And in terms of a,
00:47:53
Speaker
The recommendation, obviously, there's growing enthusiasm and some evidence for the ability to safely give vasopressors through peripheral lines, but the location of that line is probably important where you're using it just for a short period of time or not, and it has to be distal to the antecubital, right?
00:48:13
Speaker
Proximal to the antecubital.
00:48:15
Speaker
Yeah.
00:48:16
Speaker
And thank you for highlighting that because that's actually a typo in the executive summary.
00:48:21
Speaker
So there's the two publications, right?
00:48:23
Speaker
There's the full guidelines document, and there's an executive summary, and there's a typo or, you know, transposition error that we made in the executive summary where that says that they're distal to the antecubital fossa, but it should be in a vein, a big vein proximal to the antecub.
00:48:39
Speaker
That's still hard even when I'm looking at my antecubital fossa, I still get it wrong.
00:48:43
Speaker
But the idea that you want to use a larger vein.
00:48:46
Speaker
That's exactly how we made that error, right?
00:48:48
Speaker
You're like distal proximal.
00:48:49
Speaker
That's not how our brains work, right?
00:48:51
Speaker
I'm like, so I just got to remember, put it in a big vein.
00:48:54
Speaker
Yeah, closer to the heart, proximal to the heart.
00:48:57
Speaker
Yeah, exactly.
00:48:59
Speaker
Perfect.
00:49:00
Speaker
Let's talk about additional therapies and another topic that seems to be like a pendulum that goes back and forth in critical care.
00:49:10
Speaker
And even in COVID-19, we've seen that, which is the use of corticosteroids.
00:49:13
Speaker
So specifically,
00:49:15
Speaker
the recommendation for corticosteroids for shock.
00:49:18
Speaker
Yeah, so corticosteroids are funny, right?
00:49:21
Speaker
Like they weren't, well, we're never gonna stop wanting to give corticosteroids for critical illness.
00:49:26
Speaker
Like, cause we've been studying it for what, how long?
00:49:30
Speaker
25 years, 30 years, 40 years of corticosteroid study for this?
00:49:35
Speaker
So I'm actually gonna flip through the guidelines here and pull up the actual recommendations so I don't misspeak around it.
00:49:42
Speaker
So forgive me for one minute while I'm scrolling through this very lengthy document on my computer as we're talking from it.
00:49:50
Speaker
But we did, of course, again, ask the question of should we use corticosteroids for the management of patients with septic shock from that?
00:50:00
Speaker
And we issued, hang on, might wanna pause this in the actual,
00:50:08
Speaker
We issued a weak recommendation based on moderate quality of evidence that for adults with septic shock and an ongoing requirement for vasopressor therapy, we suggest using IV corticosteroids.
00:50:19
Speaker
And we define that as a typical dose at a total of 200 milligrams a day
00:50:24
Speaker
given either as 50 milligrams every six hours or as a continuous effusion.
00:50:29
Speaker
And I think that the continuous effusion is a little bit more common in the European approach than in a North American approach from that.
00:50:37
Speaker
And then the question of course is what threshold should we consider for a requirement for vasopressor therapy?
00:50:45
Speaker
Should you initiate steroids when somebody's just on a little bit of a whiff of norepinephrine still or should they be on a higher dose?
00:50:53
Speaker
And so the suggestion from the guidelines panel, again, not a formal recommendation, but the suggestion was that this could be considered at a dose of norepinephrine greater than 0.25 mikes per kilo per minute for at least four hours.
00:51:06
Speaker
So again, sort of in that moderate to high dose norepinephrine use to add corticosteroids at 50 milligrams Q6 or 200 milligrams a day, given as a continuous infusion.
00:51:18
Speaker
And so that's a weak recommendation based on moderate quality of evidence from that.
00:51:22
Speaker
And that's actually pretty similar to our prior recommendation.
00:51:24
Speaker
The big difference with this one is that we added the remark around what the panel would consider as kind of the threshold to consider adding corticosteroids.
00:51:36
Speaker
And I think it also reflects to what I think have been able to view as many people's practice, right?
00:51:44
Speaker
I think that
00:51:46
Speaker
usually it reflects what's going on.
00:51:48
Speaker
And like you said, it has a moderate level of evidence because it's been studied a lot, but what we've never been able to show is the improvement in mortality, but the quicker recovery from shock and other outcomes are there.
00:52:01
Speaker
So I think it makes sense.
00:52:03
Speaker
That's exactly it.
00:52:04
Speaker
So we're really using shock resolution as the end point there.
00:52:08
Speaker
That was an interesting piece around, um,
00:52:12
Speaker
you know, where the public members contributed to the panel was also sort of saying, like, what outcomes really matter to patients?
00:52:19
Speaker
And, you know, I was sort of interested when the public members would contribute things like they were not super interested in general in things like fewer days on dialysis.
00:52:31
Speaker
That's not an important patient-centered outcome, at least from their perspectives.
00:52:35
Speaker
They were concerned about whether you survive the ICU, whether you go home, what your functional status is, but things that we often think about avoidance of dialysis or fewer days on dialysis and that they were like, yeah, that doesn't really matter that much to me as the patient.
00:52:49
Speaker
Yeah, definitely.
00:52:51
Speaker
I think it's another great example of why having stakeholders like patients in the discussion is so important because it might redirect us to what really matters.
00:53:02
Speaker
Exactly.
00:53:02
Speaker
Exactly.
00:53:04
Speaker
The other question regarding additional therapies that I want to hear from is the vitamin C recommendation.
00:53:10
Speaker
Vitamin C obviously with sepsis and also with COVID, a lot of noise.
00:53:15
Speaker
There's been some studies now.
00:53:17
Speaker
Where does the guideline stand on this today?
00:53:20
Speaker
Yeah, so this was a new question.
00:53:22
Speaker
We hadn't asked this question in previous revisions of the guidelines.
00:53:27
Speaker
We had a new PICA question.
00:53:29
Speaker
we issued a suggestion against using vitamin C, a weak recommendation based on low quality of evidence from that.
00:53:39
Speaker
Notably, it does not include data from the recently published VICTIS trial, because that was after the censoring date for this study, for the guidelines rather.
00:53:51
Speaker
But again, it was sort of,
00:53:55
Speaker
based on looking at multiple factors in multiple outcomes, mortality, new onset organ dysfunction.
00:54:02
Speaker
And so the overall size of any desirable effect in these seven studies that we looked at in terms of the use of IV vitamin C, there really wasn't any convincing signal of benefit.
00:54:14
Speaker
The estimates of potential harm were widely variable from that.
00:54:19
Speaker
But again, probably no significant, at least in the literature we have so far,
00:54:23
Speaker
significant evidence of harm, but the absence of benefit itself led us to a suggestion against the use of vitamin C. Again, low quality of evidence, so potential future work could guide that recommendation further, but where we are now is a weak recommendation against its use.
00:54:42
Speaker
And finally, I wanted to kind of start wrapping up the clinical discussion with a new area that really, I think,
00:54:51
Speaker
not only in sepsis, but in critical illness in general, and even in COVID-19 has become very, very evident to be of great importance for our patients and for ultimately what matters to them.
00:55:05
Speaker
And that is that last section that talks about goals of care and long-term outcomes.
00:55:10
Speaker
So instead of diving into those recommendations specifically, if you could just give us maybe kind of a summary or an overview of the direction and the meaning of this section.
00:55:22
Speaker
Yeah, the, you know, the impetus to, you know, change and add and really expand this section was exactly what you said, is that I think, you know, as we, as our field moves forward, right, we are increasingly recognizing that, you know, successfully discharging somebody from the ICU or from the hospital is not the end of that illness episode for that patient, right, that there are,
00:55:52
Speaker
life-changing long-term effects from severe and critical illness, sepsis being one of them, but other, obviously, COVID, other, any other critical illness syndrome from that.
00:56:05
Speaker
And we wanted to start incorporating that into the guidelines of thinking beyond just short-term mortality as the endpoint for guidelines, recommendations, but thinking about
00:56:17
Speaker
long-term functional outcomes for patients from that.
00:56:20
Speaker
And so we asked a multitude of questions in this vein, right, around how what we do in the hospital impacts long-term outcomes for patients who survive sepsis.
00:56:30
Speaker
You know, whether looking at a wide-ranging thing, right, from structured handoff processes in the hospital to discharge planning to patient or family education about sepsis to post-ICU clinics or post-sepsis peer support groups, from that
00:56:46
Speaker
And the bulk of the recommendations are based on pretty low quality of evidence at this point in time, low to very low quality of evidence.
00:56:55
Speaker
There's several that we found we couldn't issue a recommendation because the evidence base just wasn't there, despite the entire panel and the public members thinking these are really important questions that we need to know the answers to.
00:57:06
Speaker
So I really look at this section as
00:57:10
Speaker
you know, really groundbreaking for future directions, for what we need to think about beyond short-term mortality and what we need to know and what patients need us to help guide them about is what does, what do long-term outcomes look like and how do we impact that based on what we do in the hospital from that.
00:57:31
Speaker
So I look at it really as a research agenda setting section that says, boy, we have a lot of work left to do in this system because there's,
00:57:39
Speaker
the quality of evidence that we have in that right now is growing, but it's still pretty, it's still pretty sparse.
00:57:47
Speaker
Yeah.
00:57:47
Speaker
And I think that this whole area is something that obviously we're learning a lot and that has a lot of opportunity for research, but also for improving the clinical care we provide.
00:57:57
Speaker
But I almost like when I think about this field that critical illness for our patients is a marathon.
00:58:03
Speaker
And in the ICU, we're high-fiving them when they finished the first 5K, right?
00:58:08
Speaker
Like the first three miles.
00:58:09
Speaker
and we kind of forget the risk.
00:58:10
Speaker
That's a great analogy.
00:58:13
Speaker
Excellent.
00:58:13
Speaker
Well, Laura, I really appreciate, I mean, you sharing your expertise and more importantly, appreciate the effort that goes into these guidelines and the work that you've done also with the NIH COVID-19 guidelines that I think have been such a source of reliable, good information for many, many clinicians.
00:58:33
Speaker
And we could talk about this for hours, but like we said, we arbitrarily chose
00:58:38
Speaker
a handful of recommendations that we thought would be good to start or pique the interest of our audience so they can go and dive a little bit deeper in the guidance, which will be attached to the show notes.
00:58:50
Speaker
But we would like to finish this episode with some questions that are unrelated to the clinical topic.
00:58:58
Speaker
Would that be okay?
00:59:00
Speaker
Sure, let's do it.
00:59:02
Speaker
So the first question relates to book and is there a book that has influenced you
00:59:06
Speaker
significantly that a book that you have gifted very frequently to other people?
00:59:12
Speaker
Yeah, there's so many great books I've read, right?
00:59:16
Speaker
And books that make you think, books that make you reflect, books that change your viewpoint on things.
00:59:24
Speaker
But if I've tried to pinpoint one book that says this has really changed
00:59:31
Speaker
how I approach life, that's really hard for me to do from that.
00:59:33
Speaker
So I'm gonna actually go with the second part of the question, I think, and talk a little bit about books that I've gifted to people.
00:59:39
Speaker
And there's a book that I've given to several young girls in family and friends from that.
00:59:49
Speaker
And as I find it, I think really potentially inspiring, particularly for young girls to read.
00:59:57
Speaker
And so it's called Good Night Stories for Rebel Girls.
01:00:01
Speaker
And it's a hundred sort of page long stories about groundbreaking women and what they've done from that, from Amelia Earhart to Ruth Bader Ginsburg, to Harriet Tubman.
01:00:16
Speaker
So they're very short little vignettes.
01:00:18
Speaker
It's good for people sort of early on in their reading careers from that, but I find it a great sort of inspiration to our hopefully future leaders.
01:00:31
Speaker
I love it.
01:00:31
Speaker
And I will definitely reference that in the show notes.
01:00:33
Speaker
And I think that for, for, for those, I mean, who are parents of girls or colleagues of girls, obviously learning about these stories and sharing these and becoming better allies in the workplace is going to be very important as we, as we really move forward to not only increasing diversity in our roles, but also being more inclusive in what we do at all levels.
01:00:56
Speaker
So I definitely will, I have not read that book, but,
01:00:58
Speaker
having a daughter and young nieces will definitely look into it.
01:01:03
Speaker
I hope they enjoy it.
01:01:05
Speaker
The second question relates to something that you believe to be true in medicine or in life that most other people don't believe or at least don't act as they believe it's true.
01:01:18
Speaker
I don't know if most people don't believe this or not, but take this as a little bit tongue in cheek from it, but I've been finding myself recently
01:01:29
Speaker
I'm thinking of something called Hanlon's razor.
01:01:34
Speaker
So I don't know if you know what Hanlon's razor is, but it was apparently a statement submitted to a joke book that then has sort of entered the public, the wider lexicon.
01:01:45
Speaker
And it usually gets paraphrased something along the lines of never attribute to malice that which can be adequately explained by stupidity or incompetence.
01:01:57
Speaker
And,
01:01:57
Speaker
So I've been finding myself thinking about this, you know, and I think probably as, you know, many of us have been, you know, deeply, deeply affected by the pandemic from that.
01:02:06
Speaker
And I find myself that even both personally, but also amongst friends, peers, colleagues, that I think many of us are quicker to jump to a conclusion that something has ill intent behind it rather than,
01:02:25
Speaker
giving people grace around whatever it may be.
01:02:29
Speaker
So again, that statement's meant to be a little bit tongue in cheek, but it kind of reminds me of give people grace and don't assume bad intent.
01:02:39
Speaker
Well, and it's funny that you mentioned it because I actually did not know about this till recently, but reading a book on mental models, they were talking about Oakham's racer, which is very, very well known, but they also mentioned Hanlon's racer and I was reading about it.
01:02:54
Speaker
And exactly what came to mind is a statement that I've shared with multiple colleagues when they've complained to me about difficult families with COVID-19 patients, especially in this last wave here in Texas.
01:03:09
Speaker
And what I always remind them is that the families are victims.
01:03:12
Speaker
They're not doing it on purpose.
01:03:14
Speaker
They really believe that perhaps drug A or drug B or this or that is going to save their loved one.
01:03:22
Speaker
And that's why they're fighting for that, but they don't do it with ill intention or malice.
01:03:29
Speaker
They're just trying to, they're misinformed, right?
01:03:31
Speaker
I mean, and they're just trying to do what's best for their family members.
01:03:33
Speaker
So I think it definitely, like you said, tongue in cheek, but very true.
01:03:38
Speaker
Yeah.
01:03:38
Speaker
And it just reminds me that to be more mindful about offering people grace.
01:03:43
Speaker
This has been an amazingly taxing time for everyone.
01:03:47
Speaker
Yeah, definitely.
01:03:49
Speaker
We can't be kind enough to each other, I think.
01:03:52
Speaker
And that's one way of kindness.
01:03:54
Speaker
Really, we always assume the worst of people.
01:03:57
Speaker
And like you said, ignorance or stupidity is a much more likely reason or explanation than actually ill intent or malice.
01:04:08
Speaker
Yeah, absolutely.
01:04:09
Speaker
And finally, we just want to close with what would you want every intensivist that's listening to us to know could be a quote or a fact or just a thought?
01:04:20
Speaker
Yeah, that's a hard one.
01:04:22
Speaker
The one statement that I find myself referencing quite a bit, you know, whenever I'm on service in the ICU, is a saying that I'm going to paraphrase that I learned from one of my attendings at the University of Washington when I was a fellow.
01:04:38
Speaker
So I remember David Pearson, if anybody listening knows him, used to say a statement that I'm going to try not to butcher, but I think has really good roots, which is,
01:04:51
Speaker
you know, part of the art of medicine is knowing when to not just stand there, do something, and when to not just do something, stand there.
01:05:03
Speaker
And I find myself using that, you know, amongst my ICU team as a reminder of, you know, sometimes you just need to step back and not lose your cool and know when you need to act immediately and when you just need to stand there and let
01:05:21
Speaker
things kind of settle a little bit.
01:05:23
Speaker
Absolutely.
01:05:24
Speaker
And I think that's a perfect place to stop.
01:05:27
Speaker
Laura, again, thank you for your generosity with your time and sharing your expertise.
01:05:33
Speaker
I look forward to having you back on the podcast to talk about sepsis or other topics and also look forward to seeing you in person soon.
01:05:39
Speaker
I mean, it's been obviously a couple of years that we haven't had a chance to meet with our colleagues.
01:05:44
Speaker
So hopefully that will come soon in a conference next year.
01:05:48
Speaker
Yeah, I hope so too.
01:05:49
Speaker
Thanks so much for the invitation.
01:05:50
Speaker
It was really fun to do this.
01:05:52
Speaker
Take care.
01:05:53
Speaker
Bye-bye.
01:05:56
Speaker
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01:05:59
Speaker
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01:06:05
Speaker
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01:06:10
Speaker
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