Transcript
Speaker: Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: And now, your host, Dr. Sergio Zanotti.
Speaker: Sepsis is a leading cause of morbidity and mortality in hospitalized patients and is the most expensive disease to treat in hospitals across the United States.
Speaker: The Surviving Sepsis Campaign has been working on improving outcomes for patients with sepsis for well over a decade.
Speaker: Today, we are fortunate to have one of its leaders as a guest to discuss the 2018 update, the Hour One Bundle.
Speaker: Our guest is Dr. Mitchell Levy, Professor of Medicine and Division Chief of Pulmonary and Critical Care Medicine at the Alpert Medical School of Brown University.
Speaker: Dr. Levy is also the Medical Director of the MICU at Rhode Island Hospital in Providence, Rhode Island.
Speaker: Dr. Levy is a world-class investigator, clinician, and teacher.
Speaker: He's a past president of the Society of Critical Care Medicine, a master of the College of Critical Care Medicine, and currently is a member of the Surviving Sepsis Campaign Executive Committee and is a Surviving Sepsis Campaign Guidelines author.
Speaker: Dr. Levy has published an impressive number of original studies within the field of critical care, including studies in ARDS, ethics, and sepsis.
Speaker: Most recently, Dr. Levy published the Surviving Sepsis Campaign Bundle 2018 update, which will be the topic of our conversation today.
Speaker: Mitchell, welcome to Critical Matters.
Speaker: Thanks, Sergio, and it's a pleasure to be here.
Speaker: and thanks for the invitation.
Speaker: Absolutely.
Speaker: So I would like to start for our listeners who may be new to critical care or those of whom may have been living under a rock, if you could tell us a little bit about the Surviving Sepsis Campaign and its history.
Speaker: I'd be happy to.
Speaker: The Surviving Sepsis Campaign has, I think it's a remarkable example in medicine of an initiative that really has been based on grassroots
Speaker: That is that there were over started.
Speaker: The surviving steps campaign started in 2002.
Speaker: It was a sponsorship between the Society of Critical Care Medicine, the European Society of Intensive Care Medicine, and at that time, the International Sepsis Forum.
Speaker: Over time, the International Sepsis Forum dropped off and it was just the two critical care societies.
Speaker: So in 2002, we all came together with a group of
Speaker: with sepsis experts and committed to a 25% reduction in mortality over a five-year period globally and the development of evidence-based guidelines.
Speaker: And so over the next 10 years, it took us a little longer than five years, but over the next 10 years, we have now produced four iterations of the surviving sepsis campaign guidelines, which have become the gold standard for
Speaker: management of sepsis across the globe.
Speaker: We developed the initial sepsis bundles in partnership with the Institute for Healthcare Improvement, the IHI, which is probably the premier quality improvement institute in the United States founded by Don Berwick.
Speaker: And we partnered to develop the sepsis bundles, which we implemented starting in 2005 and then published two separate publications
Speaker: in 2010 and then again in 2015, which demonstrated over a seven and a half year period a 25% reduction, relative risk reduction, in sepsis mortality associated with increasing compliance with the sepsis bundle.
Speaker: And it was out of that, out of those data, and by the way, there are now over 60 manuscripts in the peer-reviewed literature using
Speaker: the sepsis bundles or some variation of our bundles that have demonstrated an associated reduction in mortality with improved compliance with these bundles.
Speaker: And it was all of that that led to the initiatives out of New York State and now the UK and the US looking at using bundles to improve outcomes in sepsis.
Speaker: So overall, I think, and I should say that the surviving sepsis campaign implementation phase
Speaker: was on three continents in Europe, North America, and Latin America and involved over 225 hospitals.
Speaker: And as I said at the beginning, one of the things that most impressed me is the amount of academic institutions was relatively small in the campaign.
Speaker: It was an unfunded initiative in which clinicians stepped up and decided that they could do better at managing patients with sepsis and they wanted to do the right thing.
Speaker: and they were committed, even without funding, to taking part in the campaign and changing care for the better for these patients who are critically ill with severe sepsis and septic shock.
Speaker: No, and I think that from the perspective of a practicing clinician, I think tremendous utility and good has been done with not only providing these several iterations of the guidelines, but also just bringing sepsis to the forefront of our discussion, not only among clinicians, but among different specialties and the lay public.
Speaker: And I think for a disease that kills and affects so many of our patients, that was something that clearly was lacking 15 years ago.
Speaker: Yeah, I think that's exactly right.
Speaker: And I do feel that one of the things that I take most pride in on behalf of the campaign is that you could say that we put sepsis on the map.
Speaker: When we started and you asked participants in any given talk, how many of you have a sepsis initiative in your hospital or your hospital network, there would be very few hands raised.
Speaker: And now any talk you give,
Speaker: there is almost no one who doesn't raise their hand because sepsis initiatives, hospital-wide sepsis initiatives are so underpresent right now.
Speaker: And I think that one of the aspects that has always fascinated me about sepsis, Mitchell, is that obviously it's a syndrome and our knowledge about it, like everything in medicine, but I think particularly in sepsis, is very fluid.
Speaker: So this is not by any means things that are set in stone.
Speaker: And like you mentioned, the first iteration of the bundles included things at 24 hours that we don't do maybe today.
Speaker: But even then, it showed that improving compliance with a set of standards does drive performance and does improve mortality.
Speaker: And that continues to evolve.
Speaker: And I guess we're going to hear the latest evolution of the bundles a little bit later.
Speaker: Yeah, that's a very good point, Sergio.
Speaker: And I think one worth emphasizing.
Speaker: There has been a lot of controversy, as we all know,
Speaker: with the rapid adoption of some of the initiatives for which we advocated in the Surviving Sepsis Campaign.
Speaker: And many of the trials that looked positive initially later turned out to be negative.
Speaker: But I think that's very important.
Speaker: They were negative.
Speaker: They never demonstrated any evidence of harm.
Speaker: So the fact that we advocated for rapid adoption
Speaker: of research to the bedside, I think turned out to be accurate in that when we had to drop things from the bundle, like steroids or even drotrichogen alpha, it was because the subsequent trials were found to be negative, not that they caused harm.
Speaker: And that's very important as we move forward in the future that we're comfortable advocating for adoption of research while at the same time acknowledging that we have to be flexible and be prepared to change.
Speaker: Absolutely.
Speaker: So one of the things that we talk about in our group within the concept, what we call the lean ICU is flexible regimentation, being regimented in terms of having a standard.
Speaker: And by that, we don't mean a cookbook, but basically these are the four or three essential elements that every patient with this disease must get or every process in the ICU must have.
Speaker: But then be very flexible that you're operating on best available evidence.
Speaker: So when there's better evidence that might indicate that we should do something different,
Speaker: you have to be able to change.
Speaker: That's exactly right.
Speaker: So let's talk about two topics that I think are often confused and might be source of some controversy among clinicians, but I really think it's important to just defining and differentiating what they mean in relation to the Surviving Sepsis Campaign.
Speaker: The first one is sepsis definitions.
Speaker: As I mentioned earlier, it's a syndrome.
Speaker: When you say this patient looks septic, I think it might mean something different for an ED physician, for an ICU physician, for a chart abstractor.
Speaker: But also with recent publications of sepsis-3 definitions, I think there's a lot of people who are still confused.
Speaker: Any comments you can make on that front, Mitchell?
Speaker: Yes.
Speaker: The sepsis-3 definition has...
Speaker: First of all, I should say that the committee that determined the definitions, the consensus group, was, although it was from the European Society of Intensive Care Medicine and the Society of Critical Care Medicine and a host of other supporting critical care societies, it was completely separate from the Surviving Sepsis Campaign.
Speaker: So although we adopted for the last iteration of the campaign guidelines the Sepsis III definitions,
Speaker: The campaign itself really was not involved in any official way.
Speaker: Some of us who are, of course, involved in both.
Speaker: Myself, for instance, is on the Executive and Steering Committee of the Surviving Sepsis Campaign and was on the task force for the new definition, but they're really separate entities.
Speaker: More importantly, our attempt at clarification with the sepsis-free definitions, in many ways you could say backfired.
Speaker: And you actually alluded to it, although I think unwittingly.
Speaker: So for years, two iterations, in fact, from 1991 and then again in 2001, the definitions were sepsis, severe sepsis, and septic shock.
Speaker: And as we all know, severe sepsis was infection, evidence of inflammation, and organ dysfunction.
Speaker: But the truth is, and therefore sepsis was only
Speaker: evidence of infection and inflammation.
Speaker: But the truth is clinicians, just as you said, Sergio, when they thought someone was getting sicker, they said, oh, Mrs. Jones looks like she's getting septic.
Speaker: We never said, Mrs. Jones looks like she's getting severely septic.
Speaker: And so the vernacular, if you will, at the bedside was sepsis was bad.
Speaker: But in fact,
Speaker: For the definition, sepsis was not bad.
Speaker: Sepsis just was the body's inflammatory response to infection, not necessarily bad.
Speaker: It didn't become bad until organ dysfunction became manifest, and therefore a patient met the criteria for severe sepsis.
Speaker: In the sepsis 3 group, we felt that it was really time to align the consensus definitions that were in use
Speaker: with the way we as clinicians use them at the bedside.
Speaker: That is, when someone has a simple pneumonia without organ dysfunction, we say this patient has pneumonia.
Speaker: If you send someone home from your office or even the emergency department without organ dysfunction but with a, quote, walking pneumonia, close quote, you don't say this patient was septic.
Speaker: But when someone then develops severe ARDS or renal failure,
Speaker: or hypotension because of their pneumonia, we say that patient's not septic and we admit them.
Speaker: So that's exactly what the change was with the new sepsis-3 definitions.
Speaker: We went from sepsis, severe sepsis, septic shock, to what we all felt on the task force was a more accurate way in which we all use it, which is infection, that is UTI or pneumonia, sepsis, which is pneumonia and evidence of organ dysfunction, and then, of course, septic shock.
Speaker: So I still feel that change in definition was the right way to go.
Speaker: The problem is, of course, for coding, especially in the United States, the coding now in the U.S. does not match the new definitions.
Speaker: And therefore, the uptake of the new definitions nationally have been very slow in the United States.
Speaker: And I think it causes a lot of confusion with providers that are not necessarily in the ICU, but are nurses and abstractors, because what it does ultimately is it lumps a whole bunch of patients who just have uncomplicated infections within these categories that we're trying to target and creates these big denominators that make our patients
Speaker: metrics look bad, but also make the mortality probably look better than it should.
Speaker: And I think that without definitions, just to clarify, Mitchell, moving forward, when we talk about the bundles, we're really talking about applying them to patients who have a suspected or documented infection with acute organ failure or who have progressed to a state of shock.
Speaker: Is that correct?
Speaker: That's absolutely correct.
Speaker: And you're 100% right.
Speaker: We wound up causing much more confusion than help
Speaker: And that's why in the United States, certainly for New York State and at the federal government level, they have specifically not adopted the sepsis three definitions so that the coding can be clear and clinicians can be clear.
Speaker: And as you said, most importantly about the appropriate denominator, because when you add the old sepsis term, which is no organ dysfunction, when you add those patients and their mortality rate,
Speaker: to the denominator of patients with organ dysfunction, everybody's mortality rate looks better.
Speaker: So the other topic that I wanted to ask you about was the SEP1 CMS bundles, which obviously are regulatory in every hospital that I know of is working and to some extent struggling with.
Speaker: Can you just make the distinction between that and the Surrounding Cephasis Campaign bundles and recommendations?
Speaker: Yes, and this is very important.
Speaker: Now, because...
Speaker: The two bundles have been conflated, not just in the mind of the public, but a lot of the controversy now that has been directed in the literature towards the surviving sepsis campaign conflates the SEP1 bundle with the surviving sepsis campaign bundle.
Speaker: Having said that, there's no question, and I take pride in this, that the data from the surviving sepsis campaign that demonstrated association between improved survival
Speaker: and the surviving sepsis campaign bundles are what drove the New York State government and the federal government to develop their own bundle so that they could drive change in clinical behavior to be more consistent with evidence-based practice.
Speaker: But the SEP1 bundle is truly a CMS measure.
Speaker: Now, a lot of the individual elements are similar
Speaker: to what we developed in the surviving sepsis campaign.
Speaker: However, the way of identifying the patients, the time zero that they use in SEP1 are very different than the surviving sepsis campaign.
Speaker: And the SEP1 bundle is not the surviving sepsis campaign bundle.
Speaker: So let's dive into the bundles now.
Speaker: And I guess we could start by defining for everybody just to make sure we're on the same page.
Speaker: What is a bundle?
Speaker: Yeah, that's a great question, Sergio.
Speaker: The bundle concept was really developed by the Institute for Healthcare Improvement.
Speaker: And the first bundles that were in use with IHI were the ventilator-associated pneumonia bundle and the central line-associated bloodstream infection bundle, the CLABSI bundle.
Speaker: And many of that work was, as we know, done by Peter Pronovost when he worked for the Institute for Healthcare Improvement.
Speaker: and people like Terry Clemmer from Latter-day Saints and Intermountain Healthcare in Salt Lake City, and Roger Resar, who worked with IHI, were really pioneers in developing bundles.
Speaker: The idea of a bundle is you define a set of interventions that are evidence-based and founded on recent literature, and that are not being adopted widely at the bedside currently.
Speaker: And the key to a bundle is that they're grouped together in time and easy to measure.
Speaker: So any element like, let's say blood cultures, should be able to be easily chart-abstracted and answered yes or no.
Speaker: Lactate, was it measured or not?
Speaker: If so, what was it?
Speaker: And so easy to measure, yes, no is one important key to a bundle.
Speaker: And the second is that they're grouped in time closely.
Speaker: So in other words,
Speaker: If you did a bundle where you measured it every Tuesday and Thursday of the second week in a month, clearly that's gonna be a very difficult bundle to monitor and measure.
Speaker: But therefore, many of the bundles are what happens in the first three hours, what happens in the first six hours, what happens in the first 24 hours.
Speaker: So easy to measure and grouped together in an easily identifiable time period
Speaker: are the two key aspects of bundle technology that makes it work.
Speaker: So, Mitchell, do bundles make a difference in patient outcomes?
Speaker: That's a great question, Sergio, and one that I'm amazed at.
Speaker: We still ask in 2018.
Speaker: I understand that for many years, the detractors of quality improvement and in particular the Surviving Sepsis Campaign repeatedly would say, well, there's no evidence that bundles work.
Speaker: I think that
Speaker: I think one has to acknowledge doing a review in the literature.
Speaker: And by the way, there are several published meta-analyses now.
Speaker: As I said earlier in this podcast, there are over 60 manuscripts in the peer-reviewed literature that demonstrate an association between improved compliance and decreased mortality with the use of sepsis bundles.
Speaker: And it's, by the way, not just sepsis bundles.
Speaker: But even if we just stick with the sepsis bundles,
Speaker: we've published two manuscripts one with 15,000 and the other with a total of 30,000 patients in critical care medicine and intensive care medicine showing a statistically significant increase over time in compliance that was associated with a statistically significant decrease in mortality we published recently in the New England Journal of Medicine Chris Seymour was the lead author and
Speaker: A demonstration of the time to completion of the three-hour bundle was every hour delay in the completion of the six-hour bundle was associated with about a 5% increase in the odds ratio of mortality, and that was in almost 70,000 patients.
Speaker: So for me, I think we have to put to rest this question of do bundles work in the face of this overwhelming
Speaker: amount of data in the literature that demonstrate a clear association between compliance and decreased mortality for using the sepsis bundles.
Speaker: And I think it's very important also in terms of distinguishing between some refer as cookbook medicine and implementing a bundle with some key elements that all we're saying is every patient should get this within this timeframe.
Speaker: And all that happens after that really is very complex and is going to depend on the clinician and each individual patient.
Speaker: But it's just assuring the basis of what we think is critical in terms of we'll talk about the elements in a second for every patient.
Speaker: Is that correct?
Speaker: I think that's exactly right.
Speaker: And I think I hear the objections quite frequently that this removes the art of medicine and inhibits our ability to teach young clinicians to trust their understanding of their own patient population.
Speaker: And I appreciate that.
Speaker: At the same time, as we all know, medicine has gotten so complex and our lives as caregivers has become so busy that it becomes easy, honestly, to just simply
Speaker: lose track of what we're doing at the bedside and to get to do the right thing.
Speaker: So the literature is clear that prompts, electronic medical record prompts, change care for the better and so does quality improvement using standardized care.
Speaker: So I feel that I understand the feelings of loss of autonomy and what that brings to a lot of physicians and at the same time
Speaker: If my relative comes in the hospital, I want to know that he or she is being treated with standardized approach to care.
Speaker: And I think that it also speaks, Mitchell, to basic human behavior.
Speaker: What we say we will do and what we do are always two different things, no matter what the topic is, how I treat a septic patient or when I will start my diet to lose some weight.
Speaker: It's exactly the same, and I think that we need to find ways to
Speaker: overcome that inertia, overcome those heuristics and all those biases that we have in human behavior to really make sure that our patients do the best they can.
Speaker: Yeah, I think that's a very good point.
Speaker: We published a number of pieces as part of the campaign with the difference between what we think we do at the bedside and what we do do at the bedside, and I think we all experience this.
Speaker: We leave as an attending physician with a patient on a certain settings, let's say,
Speaker: ventilator settings and ARDS and we come in in the morning and you realize that for the last 12 hours their care has not at all been consistent what we would like to think
Speaker: is the best care possible for these folks.
Speaker: Absolutely.
Speaker: So let's talk about the hour one bundle.
Speaker: And I guess words do matter.
Speaker: I did notice that it's called the hour one bundle as opposed to the one hour bundle, which would be what I think most people would think about it.
Speaker: But I suspect there's an important difference there.
Speaker: Can you explain that?
Speaker: Yeah.
Speaker: Yes.
Speaker: And I'm really happy you asked this because it is,
Speaker: one of the common misunderstandings from the publication last month.
Speaker: And what we tried to do is not dissimilar to what I described we tried to do with the new sepsis redefinition, sepsis-free.
Speaker: And that is, we remember we originally had six and 24-hour bundles.
Speaker: And then we had three and six-hour bundles.
Speaker: And we, as the, and by the way, the bundles for the Surviving Sepsis Campaign come from
Speaker: the evidence-based guidelines, and they're developed by a different panel than the guideline panel.
Speaker: They're developed by the Surviving Sepsis Campaign Steering Committee, which is made up of a group of experts from the European Society of Intensive Care Medicine and the Society of Critical Care Medicine in the US.
Speaker: So we felt when you think about it, and you have a critically ill patient with sepsis, and that's in the new definition, so someone with organ dysfunction,
Speaker: and or septic shock, we don't wait for three or six hours to give them fluids, to give them vasopressors, to give them antibiotics.
Speaker: In fact, when we see a patient in the emergency department, on the wards, or in the intensive care unit, and we say, this patient's septic, we don't go through these things sequentially.
Speaker: We do them all together.
Speaker: We order blood cultures.
Speaker: We order antibiotics.
Speaker: We start fluids.
Speaker: And honestly, if their main arterial pressure is low enough, while we're giving the fluids, we start vasopressors.
Speaker: So the idea is not that all of these things should be completed within an hour.
Speaker: Of course, we have the aspiration that you'll administer the antibiotics within an hour, but we never intended that two liters, let's say two liters, 30 cc per kilogram of fluid administration would be completed within an hour
Speaker: The idea behind hour one is as soon as you see this patient, but certainly within the hour that you see a patient, all these things should be started immediately.
Speaker: And I don't think this is revolutionary.
Speaker: And it's interesting to me that there's so much controversy around it, because in fact, I think that's the way we practice, which is you see someone and you treat them right away.
Speaker: I think that's an important distinction because I do think that right now in the current environment, a lot of people are measuring when the fluids are done, when the antibiotics are completed.
Speaker: And what you're really saying here is in the first hour of recognizing a patient with sepsis, which we have defined as somebody who has an infection, either suspected or documented, and acute organ failure, we should initiate these therapies.
Speaker: And I think that's really the directive.
Speaker: I think that's exactly right now there's also controversy about when recognized in the emergency department traditionally the surviving sepsis campaign has advocated for a time zero of triage time in the ED on the wards and in the intensive care unit it is through chart abstraction and it is when recognized and I think a lot of the objection in the from my ED colleagues is well-founded because I think there's a fear of
Speaker: that they will be held to a one-hour antibiotic administration within one hour of triage.
Speaker: And honestly, I think any of us, if our loved ones came in to the emergency department, we would like to think that that might be true.
Speaker: So that's why we call it aspirational.
Speaker: The hour one bundle, there's no intention that it's going to be adopted by CMS in the United States.
Speaker: We're seeing it as aspirational to get antibiotics started within an hour and completed as quickly as possible.
Speaker: And I think it speaks very strongly to what happens with mindsets.
Speaker: And there's a lot of literature on fixed mindsets, which are very prevalent in physicians, and growth mindsets.
Speaker: But I guess the quote that would summarize the intent from what I'm understanding, Mitchell, is that to become is better than being.
Speaker: And what we're trying to do is not attain perfection, but just improve what we're doing for our patients.
Speaker: I think that's exactly right.
Speaker: I think that's exactly right.
Speaker: And honestly, I think that the experience of the surviving sepsis campaign, the data that's emerged, support that assertion.
Speaker: So if I have a patient that I recognize as having a new infection and I recognize has acute organ failure, within that first hour, what should I do?
Speaker: What are the elements of the hour one bundle?
Speaker: I think that when you see a patient and you think that they have sepsis or septic shock,
Speaker: You should immediately get a blood culture and order a pain of lactate.
Speaker: You should immediately order a broad spectrum antibiotic.
Speaker: And if they're hypotensive or their lactate comes back that quickly, you should start 30 cc per kilogram.
Speaker: And then ultimately we measure the lactate at a time interval of whatever your local protocol is.
Speaker: And if the blood pressure does not respond to fluids or like you mentioned earlier, if it's still very low while I'm giving fluids, early administration of vasopressors to protect the MAP is important.
Speaker: Exactly.
Speaker: And I think that's a... Go ahead.
Speaker: Let me just clarify because I think this is very important.
Speaker: Again, I think that if someone's not severely hypotensive and their mean arterial pressure is in the 60 range, I would start the fluids right away.
Speaker: but I might wait on vasopressors.
Speaker: But again, I don't think any of us is faced with a patient whose map is 45 or 50.
Speaker: We wouldn't just start fluids and wait to see how they responded.
Speaker: We would start vasopressors and administer fluids at the same time.
Speaker: Absolutely.
Speaker: And I think it's worth, I mean, reemphasizing that this hour one bundle applies to patients who have infection or suspected infection with acute organ failure and not to anybody who has a uncomplicated infection.
Speaker: So I think that some people do talk about this, but if you came in with unrelated symptoms and they find out you have a UTI, you do not need to do all these things.
Speaker: And I think that's a big distinction.
Speaker: And I also think, Mitchell, that it'd be worth exploring each one of these a little bit more before we wrap up.
Speaker: So let's talk about the lactate.
Speaker: What's the number that you should worry about?
Speaker: What are the triggers?
Speaker: And when should we remeasure it and why?
Speaker: Yes.
Speaker: So we kept, I think any lactate above your hospital laboratory's normal limits, which is usually 2.0 millimoles per liter,
Speaker: Identifies a patient at higher risk.
Speaker: We recently changed the definition of septic shock in February of 2016 to a lactate greater than 2.0 For the bundle we kept a lactate greater than 4.0 because we felt it identified a patient population that was at higher risk for death and we felt that
Speaker: comfortable especially because that's been the lactate level we've used up until now at keeping it at 4.0.
Speaker: So I think that's an important distinction.
Speaker: And I think the other thing that I would like you to comment on before we leave lactate behind is I see that a lot of clinicians have a hard time differentiating lactate as a diagnostic tool versus lactate as a risk assessment or prognosticator tool in terms that if you don't have infection, the lactate does not make you have sepsis.
Speaker: Can you explain that a little bit better?
Speaker: Yeah, I...
Speaker: I'm laughing only because you know, as well as I do, that we field an enormous amount of calls from clinicians who want to admit their patients to the intensive care unit because they have, quote, sepsis, close quote, as identified by a lactate.
Speaker: And I think it's really important to understand, obviously, lactate is metabolized through the liver.
Speaker: So anyone with chronic liver disease or liver dysfunction is going to have a
Speaker: chronically elevated lactate and be slow to clear an elevated lactate people with seizures obviously will have an elevated lactate there are a whole host of people with asthma can have a chronically can have an acutely elevated lactate from the acute asthmatic attack so there are a number of reasons apart from sepsis that can lead to elevated lactate and so it's very important for clinicians to understand that you start
Speaker: with a patient who you believe might have an infection, and then we obtain a lactate to determine whether this patient is either at higher risk or has evidence of severe hypoperfusion and therefore would benefit from fluid administration independent of hypotension.
Speaker: Absolutely.
Speaker: So let's talk a little bit about, I think with the blood cultures, it's self-evident in an age of resistance,
Speaker: If we can't de-escalate later, it's really difficult to manage antibiotics.
Speaker: And I think most people have no problem doing that.
Speaker: But let's talk a little bit about the antibiotics.
Speaker: What are your thoughts on antibiotics in terms of why we should give it early, how you would approach it?
Speaker: And also, you can comment a little bit of what you do as a clinician at 48 hours or later with your broad-spectrum antibiotics.
Speaker: Yes, Sergio, this is also an important question.
Speaker: As I said about bundles, I feel the same way about early antibiotics.
Speaker: I think now there are enough data in the literature, and Vinnie Liu from Kaiser Permanente in Northern California just published a really great manuscript in the American Journal of Respiratory and Critical Care Medicine.
Speaker: We've published some work out of the Surviving Sepsis Campaign, and obviously Anand Kumar published some of the original data, all of which pointed towards the fact
Speaker: that for every hour delay in the administration of appropriate broad-spectrum antibiotics, the odds ratio of mortality increases.
Speaker: Originally, the data were in only septic shock patients.
Speaker: Now they're in patients with severe sepsis or sepsis and septic shock.
Speaker: And I think the data are convincing to give antibiotics.
Speaker: I think what's important to remember is that in this era of antibiotic resistance, it's important to marry
Speaker: early antibiotic administration with antibiotic stewardship.
Speaker: And therefore, we should be administering antibiotics right away and then reevaluating right away whether or not the patient really is infected.
Speaker: So I always say to the house staff, start antibiotics right away.
Speaker: And then in the morning, let's reevaluate whether we think that patient really does have pneumonia or if it's simply congestive heart failure.
Speaker: And I feel if you marry de-escalation,
Speaker: as to rapid administration, I think that's the best combination for treating patients with suspected sepsis.
Speaker: And I think, again, we're emphasizing that this rapid administration of broad-spectrum antibiotics only applies to patients who are sick.
Speaker: Acute organ failure, suspected infection, maybe shock.
Speaker: It's not for everybody who comes to the hospital that you're sending home in terms of other diagnosis.
Speaker: What about the fluids?
Speaker: Just tell us a little bit about that.
Speaker: I hear a lot of controversy that we're flooding patients, that we're harming patients.
Speaker: People quote studies that are unrelated to adults with sepsis.
Speaker: But what is your take on fluids and what we should be doing in these patients?
Speaker: Yes.
Speaker: The amount of fluids and fluid administration is probably one of the areas which is filled with the most emotion.
Speaker: of all the things we've ever done in the campaign.
Speaker: And you're right, Sergio, the data, first of all, I have to acknowledge, there are no good randomized controlled data that show any amount of fluids are good.
Speaker: In the same way, by the way, that there are no good randomized controlled data that antibiotics make a difference.
Speaker: It's not something that is gonna be subjected to a randomized controlled trial soon.
Speaker: And the data that people use to refute the administration of 30 cc per kilogram
Speaker: are often unrelated trials in children or in under-resourced environments that really don't apply to the way in which we were using the Surviving Sepsis Campaign.
Speaker: I think there are a couple of things.
Speaker: First of all, I want to remind us, 30 cc per kilogram, in a 70 kilogram person, that's two liters.
Speaker: That's not a lot of fluid.
Speaker: And I think that for most intensivists, by the time we see these folks come up from the emergency department, they've already received at least
Speaker: two liters of fluid.
Speaker: So we're not talking about an enormous amount of fluid.
Speaker: That's one.
Speaker: Two, in the recent early goal-directed therapy trials, process, promise, and arise, before randomization, the median amount of fluid received in each of those trials was close to or above 30 cc per kilogram.
Speaker: Those are the data that we used in the last 2016 campaign guidelines
Speaker: for reasserting the value of 30 cc per kilogram since it seems to have become the standard of care.
Speaker: And finally, there are several randomized control trials now underway that are addressing this question of what's an adequate amount of fluid.
Speaker: But in the meanwhile, I think the data in the literature support the fact that it is safe, even in patients.
Speaker: And these are data from, again, Vinnie Liu
Speaker: Northern California Kaiser Permanente published in the American Journal of Respiratory and Chronical Care Medicine in which he showed that in patients with immediate with a moderate lactate elevation two to three the populations that seemed to do the best with those patients with end-stage renal disease who are dialysis dependent and patients with congestive heart failure so the data there are no data in the literature
Speaker: prospective data that demonstrate harm in those two patient populations and so the only data available in the literature support the use of 30 cc's per kilogram there's a lot of emotion there are a lot of emotional pieces written out there about the evils of fluid overload but until there are better data out there to me you we will we will save more lives to adequate fluid resuscitation and
Speaker: than by withholding fluids.
Speaker: And I think that part of the discussion, I think, that becomes muddled is that we're talking about what to do in the first hours.
Speaker: There's no question that for some time we may have gone overboard at 24, 36, 48 hours with the amount of fluids, but that's another topic and I think another challenge in terms of when people are in persistent shock, how to best manage them.
Speaker: But that's not what we're recommending with these bundles, correct?
Speaker: I think that's so important.
Speaker: Most of the data that looks at total fluid balance are looking at 72 in 96 hours.
Speaker: And by the way, the median amount of fluids that were received in the three large early gold erected therapy trials were close to eight liters in 72 hours.
Speaker: That's a totally different conversation than what we're talking about in immediate fluid resuscitation, which is in the two liter range.
Speaker: And yet, because of the emotion around all of this,
Speaker: we conflate the 8-10 liters of fluid that patients receive with a positive fluid balance at the end of admission with the administration of 2 liters of fluid within the first resuscitation period in sepsis.
Speaker: Absolutely.
Speaker: So finally, the fifth element of the bundle is
Speaker: is vasopressors.
Speaker: And you mentioned a little bit earlier how you would approach it, but can you just recap on how you would approach a patient with severe sepsis, septic shock in the first hours in terms of vasopressors?
Speaker: Yes, of course.
Speaker: So two important points.
Speaker: One, I think that there's general agreement now, especially because of the French trial and some other data, that a mean arterial pressure target of 65 millimeters of mercury is more than adequate, and there's no reason...
Speaker: to push the mean arterial pressure higher than 65 millimeters of mercury.
Speaker: And so that's the first thing that targeting a MAPA 65 is appropriate.
Speaker: The second piece, and I think this is important, is if you have someone who you're seeing in front of you, whether it's in the emergency department, on the wards, or in the ICU, and I think this is how we all practice, if they have severely low blood pressure, life-threateningly low.
Speaker: What is that definition?
Speaker: It's hard to say.
Speaker: But someone whose pressure is in the 40s or 50s, not even MAP, a systolic pressure in the 40s, 50s, 60s, or a MAP in the 50s, that patient should be started on vasopressors immediately.
Speaker: And fluid resuscitation.
Speaker: And then after the 20, 30 cc per kilogram, if you can wean the pressors rapidly, of course, I would do so.
Speaker: But I wouldn't wait until fluid administration is administered
Speaker: before starting vasopressor therapy in the face of a life-threateningly low blood pressure.
Speaker: And I think that, obviously, the timing of vasopressor is always a great challenge.
Speaker: And when we talk about it theoretically, it's sequential to after fluid.
Speaker: But like you mentioned, in reality, I think the best guide is our patient.
Speaker: And if the blood pressure is very low, like you mentioned, we probably should be doing both at the same time with the intention of weaning off as soon as possible as they respond to fluids.
Speaker: Right, exactly.
Speaker: So I think that to recap and to summarize, the hour one bundle really recommends that we take the appropriate steps to treat patients who have an infection or suspected infection with acute organ failure or those who might be in a state of shock.
Speaker: And there's five elements to this hour one bundle that include measuring a lactate,
Speaker: obtaining blood cultures, starting broad-spectrum antibiotics, administering IV fluids, 30 cc per kilogram, for those who are hypotensive or have a lactate over 4, and in those patients who are still hypotensive or don't respond initially, to start the vasopressors as soon as possible.
Speaker: Is that correct?
Speaker: I agree.
Speaker: Absolutely.
Speaker: And I would add to remeasure lactate as well.
Speaker: as part of the management strategy for the resuscitation.
Speaker: Excellent.
Speaker: So this has been, I think, a very insightful conversation.
Speaker: I think it'd be of great value for our clinicians.
Speaker: But one of the things that we also like to do at Critical Matters, Mitchell, is to tap into the wisdom of our guest and talk about some other topics that, whether they're related to the practice of critical care medicine in life, might not be related specifically to sepsis and the Hour 1 bundle.
Speaker: Would that be okay?
Speaker: Yes, it is.
Speaker: So the first question is, what book or books have influenced you the most, or what book have you gifted most often to others?
Speaker: There are so many, but for me, clearly, the book that has had the most impact for me and the one that I recommend the most is a book called The Sacred Path of the Warrior, and it's written by a Tibetan gentleman, C. Sivak.
Speaker: M-U-K-P-O, and that's the book.
Speaker: In fact, I just saw one of my physician colleagues today who I recommended that book strongly to.
Speaker: So we will definitely put that in the show notes and encourage our listeners to pick it up.
Speaker: The second question, Mitchell, is what do you believe to be true in medicine or in life that most other people don't believe?
Speaker: Well, I'm not sure I would say that this is something
Speaker: that most people other that don't believe, but I, I think we create the light life we lead.
Speaker: And I think that if we, if we reside in cynicism and skepticism, then we will lead a cynical skeptical life and be met with that.
Speaker: If we lead a life that believes in the goodness of other people and trusts,
Speaker: the profound goodness that is inherent in the human spirit.
Speaker: That's the kind of life we will lead.
Speaker: And that's the kind of environment we'll have around us.
Speaker: So we create the life that we lead by the way we live.
Speaker: And I think that that's a great point.
Speaker: I'm a big fan of the Stoic philosophy.
Speaker: And Marcos Aurelius was one that would often say that our life or our thoughts are our life.
Speaker: So what we think and what we act depends on that is ultimately how we live.
Speaker: And I think it really speaks to that as well.
Speaker: Yeah, that's right.
Speaker: The final question, Mitchell, as we close,
Speaker: would be what would you want every intensivist or every person who listens to this podcast to know yeah I like this question actually all three river I think the most important thing and something that I talk with my fellows about is the essential importance of collaboration in intensive care because the quality of the quality of care that patients receive the quality of the environment in the intensive care unit and the quality of life in
Speaker: for the clinicians in the intensive care unit is really based on our ability to collaborate together.
Speaker: And that's something that I have used to build intensive care units wherever I've gone and done that collaboratively with my nursing and respiratory and partners.
Speaker: And I feel that's the most important thing for intensives to remember.
Speaker: And I think it's not only important for intensive, it's probably for all of us in society these days.
Speaker: And perhaps the greatest enemy to collaboration is ego, which seems to be prevalent among our colleagues and in other sectors as well.
Speaker: So I think that those are very good words of advice, Mitchell, to finish.
Speaker: It was a great pleasure to have you on Critical Matters.
Speaker: I really enjoyed it.
Speaker: It's an honor to be here.
Speaker: Enjoyed our conversation and hope to have you back soon to talk about sepsis or many other topics.
Speaker: Thank you very much for your time and for sharing your knowledge with us.
Speaker: Thanks, Sergio.
Speaker: Pleasure to be here.
Speaker: Thanks again for listening to Critical Matters.
Speaker: Make sure to subscribe to this podcast on iTunes or Google Play.
