Thank you all so much for coming. I am Alice Gallo. I'm an intensivist at Mayo Clinic in Rochester, Minnesota. And I'm very honored to be here with my colleagues today. Do you want to introduce yourselves? I'm Anjali Kapoor from Cleveland Clinic. I'm Ryan Nguyen from Loma Linda University in California. We are missing our fearless leader, Dr. Viren Koh, because he got stranded last night in New York. He should be on his way to Hawaii, so hopefully he'll be here for his award this afternoon at the opening ceremony. But I'm going to try to go over what he wanted to convey to all of you. And we will save some time for questions at the end. So we would love for you to talk to us about this important topic at the end of the session. And again, thank you all so much for being here so early in the morning in this beautiful Hawaiian weather. So what Viren wanted to talk to you about was in a little bit of evidence update and outcomes from the use of different fluids. He always likes to start with a quote, and what he wanted us to take from this particular one, what he wanted to take from this particular one was that what we've been taught our whole lives is that, okay, someone doesn't look good, or they are a little dehydrated. Fluids should solve everything, right? No. And again, in this first 10 minutes, I'm representing Dr. Cole. He is the division chair at Cruz Health, and he's on his way. So a little bit of history of fluids, because again, V loves history. So we started in 1832 with IV salt solutions for color. And 2000, we went all the way down with, yes, albumin, ethyl electrolytes, albumin quantities at Pearl Harbor for blood fractionation. And also in 1932, the first time that balanced solution was used by Hartman. And then we all know early goal-directed therapy in 2001. And this is a quote by Rivers himself saying that the quantity necessary to be injected will probably be found to depend upon on the quantity of serum that's lost. And again, if you think about sepsis and septic shock, we really don't know how much has been lost. But again, we have been working with all of these colleagues who taught us about fluids initially. So strong ion difference, the Stewart method in the 80s, pH is not only determined by the hydrogen ions and bicarbonate, other ion solutions influence pH. So again, we have the dependent variables, the independent variables, and the water dissociation equilibrium in all electrical neutrality that, let's be honest, at bedside, we're not going to be thinking about this. And what we probably want to achieve is electrical neutrality. Some studies that Dr. Cole wanted to just emphasize a little bit on, that early 2012 in JAMA, we had single center studies comparing chloride liberal fluid with chloride restrictive fluid. And even back in 2012, 11 years ago, we already saw that, yes, no different mortality, but less acute kidney injury and less RRT in the chloride restrictive fluids. Same thing, they extended the before and after, and similar outcomes were seen. And then 2014, sepsis in the ICU, patients requiring pressure, so septic shock, severe sepsis, and the balance group had lower in-hospital mortality, but no difference in AKI and RRT need, or ICU length of stay. And then for non-traumatic open abdominal surgery, balance group, lower major complications, lower blood transfusion needs, and lower needs for renal replacement therapy. And then for interventional data, and again, those studies were not interventional, they were just observational. So for interventional data, AKI need for renal replacement therapy and mortality, all of the studies consistently showing that balanced solutions have, in theory, better outcomes. And then for the split RCT from 2015, what they wanted to look was the effect of buffered crystalloid solution versus saline on acute kidney injury in patients in the intensive care unit was a cluster, randomized, double crossover trial, very large population, and the weakness was normal saline exposure was small, about 2 liters, which in reality, for those of you who practice in the ICU, you know, by the time patients reach the ICU, they already received way more than 2 liters of saline-containing solutions. But again, no difference in acute kidney injury, in-hospital mortality, or renal replacement need in 90 days. And then 2017 critical care medicine, chloride content of fluids used for large volume resuscitation is associated with reduced survival. So again, hyperchloremic-containing fluids and hyperchloremic acidosis was a thing and did increase mortality and hospital mortality, mortality within the ICU admission, and also worse kidney outcomes. Unadjusted outcomes, again, just noticing that mortality after ICU admission was also worse in the chloride, high chloride-containing fluids. So for every 100 mL equivalence increase in chloride load, there is a 5.5% increase in mortality at one year. Again, for this particular study, large population, there was no association with AKI after controlling for APS3. So treating shock, do we do balanced fluids? Do we do saline? What should we do in 2023? So the SALT-ED from 2018 was non-critically ill patients. Again, no difference in hospital-free days or in hospital mortality, but significantly lesser with balanced fluids, the MIG-30 score. SMART 2018 critically ill patients were included. Again, the MIG-30 score was way lesser in balanced fluid, patients who received balanced fluid and no difference in mortality, but again, no difference in the need for neuronal replacement therapy and no difference in ICU-free days. Then New England last year, by ACE-MET analysis, average effect of balanced fluids versus saline was reduced mortality. Let's talk about pancreatitis, balanced fluid versus saline. Same thing, the patients who received the balanced solutions had less necrosis and less fluid collection. How about DKA? Shorter time for DKA resolution, shorter time to stopping insulin for the balanced crystalloid group. So, in general, chloride is the problem. So, consider balanced solutions. Obviously, obviously, there are several particular situations, and again, for those of you who have heard me speak before, I'm a big proponent, and I can represent Dr. Cole on this one too, of individualizing everything. But again, if your patient doesn't have brain trauma, if your patient is in your ICU because of sepsis, pancreatitis, they probably will benefit more from balanced solution than chloride-containing solutions. So, consider balanced solutions. And please don't forget to evaluate session in the app, and if you wanted to tag Viren, he's at Viren Cole, MD. Thank you. You should be good. You should be good. So, the next is, we decided balanced fluid, but how do you give? Do you give it to everybody, or you, how much you give and when do you stop? So, Anshul Kapoor from Cleveland Clinic, no disclosures to disclose here. I just want to comment, like this conference, for the safety of our presenters and attendees, I urge ACCP to commit to ensure that future meetings are held in locations where elected leaders understand the importance of freedom and sanctity of the patient-physician relationships. So, as I said, what we are going to discuss today is, recognize fluid responsiveness doesn't always translate into give more fluids. Appraise fluid tolerance before giving fluids to prevent fluid overload, and determine hemodynamic phenotypes of the patients and hemodynamic coherence before giving fluids. We'll talk about them one by one. So, going back to Dr. Coleslide, when did fluid start? So, it's a story which started in 1832 when Dr. Latte observed and witnessed the magic of fluid administration, and he beautifully and dramatically described, as a letter to editor to Lancet, saying, after multiple boluses, over 2.8 liters, soon the sharpened features, sunken eyes, fallen jaw, pale cold, bearing the manifest imprint of death signet, began to glow with returning animation and pulse returned to the wrist. So, this was a lady who actually responded to fluid disoxidation for the first time in history. And that's where our story goes to 1832 till now, and we are still debating what to do. So, the evidences, you know all, our landmark trial, reverse trial, which came as early goal-directed therapy as a golden hour of first six hours in ED, how to resuscitate septic shock, or SERS, patients coming in with SERS, how do we resuscitate and how the practice should go along. Here we are talking about fluid responsiveness and fluid tolerance. I'll not go into detail, but I'm just trying to make a story where we are now. So, this study did show that early goal-directed therapy is associated with increased CVP, lower lactate, lower base deficit, and lower critical illness towards the end of resuscitation and improved survival. So, when this study came out, all of us were excited that we found a solution. Ten years later, we started debating again. There were multi-center international trials at different countries came through in Australia, London, and US. Again, questioning the early goal-directed therapy. We cannot compare head-to-head these trials because the patient population was different. There was a big time lag between the early goal-directed therapy published in 2001 to these trials almost a decade after. Started in 2008, published in around 2013 and 14. So, by the time there were so many confounding factors, the overall mortality with sepsis continued to decrease with multiple interventions around the globe. More patient education, sepsis survival bundles, early administration of antibiotics, preventive care, 24 administration of intensivists. Multiple, multiple things were going along when these trials came through. If we overemphasize the results, which has multiple limitations, they all showed there is no change in mortality when you do early goal-directed therapy. But what we are trying to tease out from these studies were that they were not head-to-head comparison. The patient population was different. The time was 10 years later. And also, the mechanisms, how they did early goal-directed therapy was very different than the reverse trial. But what it led to open up is that maybe early resuscitation based on hemodynamic profile is not the way to go. In other ways, that early goal-directed therapy was done to improve sepsis outcomes. But how these trials interpreted or the people or the observation studies in between, how it interpreted early goal-directed therapy was these are the hemodynamic endpoints we have to achieve by transfusion, by pressures, by fluids. But that was not the goal of the study. We interpreted the goal of early-directed therapy wrong. So further came along, now we are criticizing fluids here. So fluid overload and mortality in adult critically ill patients, systematic review done in 2020 showed the cumulative fluid balance in different patient populations with sepsis, AKI, respiratory failure, leads to increase in mortality. To be precise, the risk of mortality increased by a factor of 1.19 per liter increase in positive fluid balance. Rang a bell that maybe not too much fluid is a good idea. So now reverse it. What happens if you keep the negative fluid balance? So again, these are very direct studies. They are not looking at other factors which are pointing towards like which are contributing to mortality of these patients. They are just looking at negative fluid balance. So at least one day of net negative fluid balance in at least first three days of treatment was associated with change in mortality. Again, these were the studies. I'm not going to take these studies into practice as such because they had multiple flaws and limitations. But the point they came across is that we have to challenge the fluid, how much fluid we are giving and how to assess how much fluid is the right amount of fluid. So what I'm saying, people were thinking the same thing, that this is the time to have fluid stewardship along with antibiotic stewardship for sepsis. So multiple reviews were writing on what are the right principles, how to guide fluid. Fluids were considered as drugs. Too less is bad. Too much is bad. Same with duration, how long we should be continuously resuscitating these patients. What is the right dose and when do we deescalate? You're going to learn more after me, the desuccitation concept. So same time, they started dividing sepsis into different stages. The resuscitation phase, optimization phase, stabilization and evacuation. Again, telling that there are different stages, the fluid requirement would be different and will be a point where we are removing the fluids from these patients. How do we define the stages is a challenge, right? When stage one turns into stage two to stage three and stage four. So while we were debating all this, in parallel, there were concepts of fluid responsiveness going along, like how do you find this patient is fluid responsive? So by definition, fluid responsiveness is defined by increase in stroke volume or cardiac output of 10 to 15% with the provision of IV fluids. So when you give preload, your cardiac output should increase by 10 to 15%. If that is happening, that patient is fluid responsive. Felt very simple. Let's do this and continue. So a plethora of literature defining how to find fluid responsiveness, how to assess what tests we can do was emerging alongside. So if you see, I did not put all the parameters because as an intensivist, we do that in day-in, day-out practice. But what I wanted to point out is the blue bars are the tests where we are mimicking fluid given, given fluid. It could be, for example, passive leg raise. We are increasing plethora by doing passive leg raise or mini fluid challenge. So all these tests have advantages and limitations. For example, these two tests I just mentioned, passive leg raise, mini fluid challenge can be done on any patient. Doesn't have to be mechanically ventilated patient. Bars in green, they do, the tests have more specificity and sensitivity if the patient is mechanically ventilated and paralyzed and supersedated, right? Pulse pressure variations, systolic volume variation, IVC distensibility. Then there are tests which can do like tidal volume challenge, increasing the tidal volume and seeing whether this patient has preload dependence. So all these tests are emerging in literature and we are using them more and more, not as a single test but in combination to assess fluid responsiveness in critically ill patients. So while we are dancing this dance of fluid responsiveness, what are we forgetting? We are just looking into equation on the left. Like when we give preload, how we are increasing the cardiac output. But what we are forgetting or what is our blindsided side is the right side of the equation, our whole venous capacitance system. We are not looking at that. We are giving fluid and looking at cardiac output. What is happening in the venous circulation or the right side of the equation is missing here. So that's where our concept of fluid tolerance comes. So fluid responsiveness can turn into fluid overload any time in the spectrum of sepsis and septic shock if we do not pay attention to fluid tolerance. So now we'll say what is fluid tolerance? It's a qualitative assessment which gives us trouble, right, because quantitative we are really good at math. It's a qualitative assessment and is defined as capacity to accept additional IV fluids without causing any downside, without causing fluid overload. So again, if you look towards the venous system, so we all know our capacitance system is large. 70% of the blood volume stays in our venous system. And 20%, 10% is in the arterial system. When we are increasing the preload, we are causing tension on the venous side of our equation. So the fluid tolerance is a venous congestion and can cause organ dysfunction and can perpetuate the cycle of capillary leak and further fluid overload. Fluid tolerance comes in to fill the continuum between fluid responsiveness and fluid overload. So how it does that? So there is a concept of microcirculation dysfunction. So what happens is when you give too much of preload, it causes microcirculatory failure. That is a stage we call flow responsiveness, in responsiveness. What happens is it could be different mechanisms. So the hypothesis is when you increase the preload, especially in encapsulated organs, for example liver and kidney, because of increased congestion, increased passive congestion in those organs, there is a decrease in flow because there is decrease in flow because of passive congestion. Or passive congestion causes increase in afterload of those organs, decreasing the inside perfusion. By decreasing the perfusion, you are causing more microcirculatory damage. The glycocalyx damage, increased vascular permeability, increased congestion, and further leading on to multi-organ dysfunction. So that term is called hemodynamic incoherence. Hemodynamic coherence is when you are giving fluid, flow is being responsive to you. You are giving fluid, patient is hemodynamically unstable, giving fluids, is translating into increase in cardiac output, and the body is tolerating the fluid. That is called hemodynamic coherence. Once you break that coherence because of passive congestion, then increasing fluid does not correlate to increase in cardiac output. Rather, it caused more damage and more venous congestion and fluid intolerance. In clinical world, how we see it, increased CVP, increased extravascular lung water, peripheral edema, more ascites. So those are the factors clinically you will look at that this patient is fluid intolerant. Hold on to that thought. What we are trying to say here is we are going to prevent that by assessing fluid intolerance beforehand. We are not going to say after developing all those components that my patient is fluid intolerant. If you give a pause, what are the factors which contribute towards fluid intolerance? There are modifiable factors. There are non-modifiable factors. So this is your protoplasm of the patient. The patient you are walking into the room with are non-modifiable factors. Age, comorbid conditions, could be structural heart disease, bad COPD, basically where the heart and lung interactions are compromised. Severity of initial circulatory dysfunction. So you cannot change those factors. You are walking into those factors. Modifiable factors are sepsis. While you are treating sepsis, these could be modified. You are walking in the first hour, there will be major capillary leak, inflammation, endothelial dysfunction, glycocalyx dysfunction. And maybe this patient you are walking in is not adequately resuscitated. So your approach to these modifiable factors will be different and would be dynamic as the disease spectrum goes along. This is directly coming from this position paper of fluid intolerance. So what is our target? If you look towards the end, it's overt organ dysfunction. I am sure we all know before we reach there, there are multiple signs which probably many of us ignore. We see overt organ dysfunction in septic shock, but maybe there are overt signs before in terms of venous strain. When the passive congestion is happening, our patient is intolerant, there's underlying venous strain, which is not clinically visible, but there are multiple investigations you can do to find that pattern of strain and stop there, stop fluid resuscitation right there and prevent. So, there is a window of opportunity right there where you can prevent further fluid resuscitation and prevent overt organ dysfunction. So, how to assess? Multiple things. It's kind of a whole body examination multiple times a day. Sequential, multi-modal clinical assessment by history, physical exam, radiological data, chest x-ray, invasive monitoring if your patient has CBP, PA catheter, thermodilution, multiple hospitals have various instruments these days, LITCO, PICO, like howsoever you want to assess, extravascular lung volume, global and diastolic volume, and POCUS, right? So, goal is like you will see all these parameters on the left side, how you assess fluid tolerance, could be PA pressure, extravascular lung border, global and diastolic volume, lung ultrasound looking for B lines, and echo of the heart, right? Tissue Doppler, E to E ratio, and mitral Doppler, E by A ratio. On the right side, you can do CBP, intra-abdominal hypertension, femoral vein Doppler to look for pulsatility, global and diastolic volume on the right side, IVC distensibility, vexus, right? So, these, some of them are old, some of them are emerging concepts, but combinedly you do all that. So, again, as we all say in critical care, one test is not the right test. When you do multiple assessment and come to same conclusion, looking at all these that this patient is fluid intolerant, that's where you stop. Last slide. So, what we are trying to do here is, we want to look at the hemodynamic coherence or incoherence, and looking at where my patient is, like, x-axis is fluid responsiveness, y-axis is fluid intolerance or tolerance. So, if you're in the green box, you're good. Patient is fluid responsive, fluid tolerant, go for it. Whatever your assessment tells you about fluid responsiveness, you are okay to give fluid. Yellow box, fluid unresponsive, but your patient is fluid tolerant. So, based on the condition, based on the stage of septic shock, based on vasoplegia, based on capillary leak, be cautious, but you can still give some fluid. Red is the zone where both are not there, non-fluid tolerance, no fluid unresponsiveness. These are the patients where you start early pressures. Gray is the zone which is blindsided by us. Patient is fluid responsive, but is intolerant. That's what we are aiming for. Because if patient is fluid responsive, but not tolerant, continuously giving fluid to those patients will turn into fluid overload and multi-organ failure. So, our goal here is not to just look at Frank-Starling curve and look at the left side of the heart. Our goal is to also look, this is a concept came through where we are looking at extravascular lung water by Mark-Philip curve. So, combining both curves together, combining the both data together and decide how much fluid our patient needs. And when my patient is fluid intolerant, that's the time to stop. So, key takeaways, relationship between static markers of cardiac filling pressures and total vascular volume is poor. Fluid should be given in the context of both fluid responsiveness and tolerance. Patient's hemodynamic phenotype, those four boxes, can change during the course of illness. Keep that in mind. You cannot have one assessment and go with it. Patient might be intolerant now, but might become tolerant as the capillary leak is reversing. Dynamic assessment of fluid tolerance should guide your resuscitation strategy. Thank you. Okay, thank you, everyone, for being here so early. I think my lecture can turn into a pro-con debate easily, but my part is to share with you when should we start vasopressor. I'm Brian Nguyen. I'm at Loma Linda University in California, and I have no disclosure. So we talk about the four stages of resuscitation and just review salvage, optimization, stabilization, and de-escalation, or in sepsis, recently in JAMA, I think it's a nice article about fluid therapy. It's about also resuscitation, optimization, stabilization, and evacuation. The topic that I'm sharing with you is when do we start vasopressor? Is it early versus late? In the early resuscitation, what we call either salvage, resuscitation, rescue, this is the early phase, not de-escalation. So what does the sepsis guideline share with us? It says, basically, there is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 hours. And this is 2021. So I'm going to share with you a few data. This is not comprehensive, but there are pros and cons to this debate. So we know that some studies show that early vasopressor is good, low mortality. This is one particular study showing that in the early vasopressor group, there's definitely less fluids and also less mortality. And in the Kaplan-Meier curve there, in the very early vasopressor group, definitely 20-day mortality is improved. This is a recent systematic review. Now keep in mind, single-center studies. And we look at timing of vasopressor anywhere from less than two hours, 93 minutes, definitely within the first six hours, or even within the next hour, basically within the first hour of triage, or even before that first fluid bolus is given. And the systematic review suggests that early vasopressor is good, decreased mortality when odds ratio of about 0.41. Now on the con side, there's study also showing that early vasopressor is bad. This is one study looking at the initiation within one hour of fluid loading of a vasopressor. It's a prospective observational multi-center in Korea, 16 hospital. It's a registry data over several years. And they look at sepsis-3 criteria. And the initiation of vasopressor within one hour suggested there was actually increased mobility. So three days later, the SOFA score is actually higher, lactate is higher, 28-day mortality is higher, 47% versus 33, ICU mortality is higher, and also hospital mortality. Now this is another study that I don't think a lot of people pay attention to. This is 33 hospitals in the United States. So this is not single-center data, over 1,600 patients, and in-hospital mortality of 31%. And you can see that this is the graph shows plotting between total fluid versus vasopressor, such that a patient who had a maximum of three liters of fluid within six hours and only five microgram of norepinephrine had actually the lowest mortality. So there's no fluid at all, and we just start vasopressor, very high dose. The mortality is up to 50%. So every 10 microgram per minute increase in norepinephrine was associated with 33% increased osteo-mortality. As fluid volume increased, the association between vasopressor and mortality decreased, such that you need at least about two liters of fluid for this association to go away. This is another recent meta-analysis, even in heart failure patient. I'm sure we're very fearful of fluids in the heart failure patient. But the systematic review actually suggests that a patient who had 30 cc per kg of fluids actually had a better outcome, with a mortality of 1.81 if we were not able to give at least 30 cc of fluid in the heart failure patient. Now as we know, this is the recent study. Basically it's a randomized study, so these are not observational study, the CLOBOS trial. Just briefly, it's a 60 US center funded by NIH over a four-year period. Randomized adult patient within four hours of sepsis, induced hypotension, refractory to that first one to three liters of fluid. So they separate into a restrictive fluid protocol and a liberal fluid protocol. Preferable vasopressor is acceptable. Importantly is that they plan to enroll 2,300 patients, but only enroll about 1,500 patients. And it was terminated after the second interim analysis for futility. So that suggests that if we had completed the study, perhaps the restrictive arm may have had higher mortality. But importantly is that there's no outcome. No outcome benefit. I know it's a busy slide, but the point is that to the left there, all the various subgroup analysis, various outcomes, secondary outcome, there was no difference at all with respect to Forrest's plot. But one comment in the paper is that in a post hoc analysis, we identified that 67% of patient in the restrictive fluid group and 59% in the liberal group were admitted to ICU. Basically, there was an 8% increase in ICU admission in the restrictive arm. To follow that, so that was an ED study. This is an ICU study. Once the patient is now admitted to the ICU, should we continue with restricting or liberalizing fluids? International study over a few years period. It's a European study, adult patient with septic shock within 12 hours before screening. And these patient had a lactate grain tube, ongoing vasopressor. So basically, they met the septic shock criteria for the sepsis 3 definition. And they already had one liter of fluid in the previous 24 hours. They randomized about 1,500 patients. And no survival benefits up to 90 days later when we're restricting fluids in the ICU. So a more recent, very update analysis that include those two randomized New England Journal study comparing lower versus high fluid volumes, and it's still in press at CHAS. And we look at quite a few number of studies, 5,600 records were initially screened, nailed down to about 13 studies, including those two recent randomized study. And there was no difference at all in mortality across the various studies when we look at the fourth plot. Also there's no mortality difference in the subgroups, importantly, as well. So as a result of those study, the pro-con debate between fluid or no fluid, this is a recurrent case example that I see today. I'm an intensivist. I also work occasionally in the emergency department, as well. But this is coming from an ICU perspective, a 72-year-old female presented to ED with evidence of severe CAP. He has a fever, tachycardic, tachypneic, blood pressure 82 or 48. He's got left lower lobe crackles. His white count 18, lactate 3.8, current 4.3. Patient received one liter of LR and broad spectrum antibiotic. Repeat lactate is now 2.8. Blood pressure dropped to 85 over 42, and norepinephrine got started. So patient got one liter and got started with norepinephrine. And obviously, when the patient is starting to raise the pressure, we have committed the patient to ICU. Patient admitted to ICU, repeat lactate is 3.4, blood pressure is 80 over 45. So now you see that lactate went down and now went up again. We continue with two more liters of fluid and also maintenance, and norepinephrine titrate off after several hours later. Patient was then transferred to the ward within 12 hours of ICU admission. So the question is, could ICU admission have been avoided if this patient had received more fluids prior to starting vasopressor? And my answer is that the fluids or suppressor sepsis is not that simple. And this editorial I was invited to write, hydrophobia does not pay. The debate of fluids versus vasopressor is on the brink of taking us back several decades when the management of sepsis was to start a fluid bolus, administer rosepin, and initiate dopamine. But I remind myself that we have made significant advances. Now it's one liter of lactate ringer, administer vancomyxosin, and initiate norepinephrine. And if some of you have been here about 20 years or plus, which I have been, we remember the adage, leave them fed and leave them dead. Is this what we want to do today? Now a reasonable approach, I think this is a concept that was recently published by Monet et al in Europe. So his suggestion is that we need to assess the patient, is there life-threatening hypotension? And perhaps look at the diastolic shock index. If it's less than, if the diastolic pressure is less than 40, or the diastolic shock index, which is heart rate over diastolic pressure, is greater than 3, where do we get the 3? I mean, that's basically arbitrary, but more physiologic. And or high risk of fluid overload. And this is where the fluid tolerance versus fluid responsiveness comes in, a clinical judgment. And if it is yes, then that basically suggests vasodilation. Then perhaps we can start norepinephrine rapidly and continue fluids. But if it's no, then the patient may not have vasodilation and continue with fluid resuscitation at vasopressor a little bit later. So that perhaps may be a good balance. And so what is this concept? Systolic shock index is basically a heart rate over systolic blood pressure. But importantly is that diastolic blood pressure may indicate a vascular tone, such that the shock index itself, diastolic shock index, may reflect the severity of circulatory dysfunction due to systemic vasodilation, dilatation. And this is a study that shows that the increase, the higher the diastolic shock index, the better the outcome. The problem is that whether this index could be used as a trigger to direct therapeutic intervention in septic shock or sepsis-related cardiovascular dysfunction deserves future research efforts. So my conclusion is the timing of fluids and vasopressor should be individualized. There's no one-size-fits-all. Continual reassessment of hemodynamics is important. Early vasopressor does not improve outcome. Vasopressor prevalence or the fear of fluids, hydrophobia does not pay. Perhaps using the diastolic shock index may be a good indicator, but that deserves further study. Thank you so much for your time. So what we've learned so far, chloride is the problem. We are not sure how much fluid to give, but we have a lot of tools to evaluate people and we should make sure that we have our patients in a place where they are still fluid-responsive but not overloaded. And early pressors might be good in some people but might not be good to others. So individualized pressor starting. The only thing that I'm pretty sure all together is that they should be de-resuscitated because the three of us talked about it and V would have talked about it too. Again like I said before, I am Alice Gallo. I'm a Mayo Clinic. I have nothing to disclose. You can find me on all social medias you like except for Facebook. I'm on Instagram. I'm on threads. I'm on Twitter. I still call it Twitter. Please send your questions and things like that and comments. Don't know what this is, but anyways. So what I want to talk to you about is about the importance of de-resuscitation. Recognize when de-resuscitation is needed and plan for the most appropriate de-resuscitation strategy for your patient. And for the purpose of this talk, volume overload means intravascularly too much fluid. And fluid accumulation means someone who needs de-resuscitation, okay? So we're talking about fluid accumulation. I like to go to bedside, so I'm trying to bring you all to bedside. We are all taking care of a 42-year-old patient admitted with septic shock from pulmonary sores three days ago with someone who was previously healthy, traveled to a large conference, ended up getting a bug, got infected. And you come on service three days after this human was there, had been resuscitated. And this is the graph that you get for your cumulative fluid for your patient. You can see that there are about 10 liters of fluid positive. And again, made a point of saying like crystalloids for the first day. And then all the medications, again, the early antibiotics that we all could agree on. The vasopressors, maybe not. They are still needing. But they're 10 liters up, and they look like this. I'm an 80s kid. I decided to choose the marshmallow man because I'm pretty fan of the Ghostbusters. What's the problem with fluid accumulation? Basically, if someone has too much fluid in their body, every single organ system will be affected negatively, potentially, with time. So think about abdominal wall. Again, marshmallow man, basically, all the walls are swollen. And that's also happening in intra-abdominal organs. It's happening in the heart. So conduction disturbances in the heart. The visceral system, again, if they are already on tube feeds, they might not be absorbing all the nutrients that you think they're absorbing. If they're still getting oral medications, they might not be absorbing those medications. So basically, fluid accumulation can affect every single organ system. And obviously, again, pulmonary care and sleep, ARDS, very well associated with fluid overload and volume accumulation. And then I just want to say all the QR codes for my references are there. So you can just get your phones and download the papers to your phone if you want to. So this was a meta-analysis done looking into randomized control trials or pseudo-randomized control trials that had looked into conservative fluid strategy versus liberal fluid strategy in patients with septic shock and ARDS. They wanted to see if ventilator-free days were different. And you can see that ventilator-free days favored conservative fluid strategy. They also wanted to see if length of stay was affected by conservative versus liberal fluid strategy. And you can see that conservative fluid strategy also showed favor to length of stay, ICO length of stay. So fluid accumulation likely not optimal. So what is deresuscitation? Like, why are we even talking about this? So what we need to do as intensivists is to start thinking about it as soon as our patient is resuscitated, as soon as they are not fluid responsive anymore, as soon as we have a good grasp of their hemodynamics, again, whichever way you use to determine hemodynamics and fluid responsiveness, that's when we need to think about actively removing fluid and actively thinking about concentrating solutions. Do they really need all the tube feeds they're getting? Is it time to de-escalate antibiotics, both in the sense of volume of antibiotics and number of antibiotics they still need? So both things, removing fluid and actively thinking about fluid solutions that are being given that we can't take away, can't stop. When do we start? As soon as resuscitation is considered completed. So again, got someone from the ED, they already got their IV fluids, they are getting their pressers, they are on antibiotics. Again, do they still need three antibiotics? Do we have cultures back? Is it time to remove one of the antibiotics so it's less fluid? And as soon as accumulation of fluid is associated with any organ dysfunction. So again, if your patient come, if you start seeing your patient and they already look like the marshmallow man, it's time. So think about these things. If they are having conduction abnormalities, think about that the heart might be having some fluid accumulation as well. If their LFTs are going up, INR is going up, is it just the sepsis and septic shock or is it the liver that's getting congested? So again, think about all the organ systems and fluid accumulation in all of the organ systems. So I didn't have a phone, what's happening? Okay. So what is the art of the resuscitation? We want to prevent fluid creep, like I just said multiple times. Think about fluids that you can stop. Think about ways of decreasing the amount of fluids your patient is giving. I personally am a big fan of early inotropes and association of vasodilators if patients are already resuscitated to try to get fluid off of them. So think about that. Think about diuretics and think about diuretics in the sense that remember there are several classes of diuretics. Lasix is great, but it's not the only diuretic we have. So make sure that you think about different diuretics that can be combined and help you in the mission of de-resuscitating your patient if they are already looking like the marshmallow man and already having end organ dysfunction. Call for CRRT early. I'm talking about ultrafiltration. Even if they don't have indications for dialysis, if their electrolytes are okay, if you did a good job and their electrolytes are okay, ultrafiltration will help decreasing those 10 liters that our patient had when we first came on service 10 minutes ago. So the art of de-resuscitation is also multimodal and includes, again, removing fluid and thinking about things that you can stop. So my take-home points for you, fluid accumulation syndrome leads to all organ dysfunction and as you saw, poor prognosis, poor all ICU prognosis. Any fluid accumulation can lead to fluid accumulation syndrome. So again, think about it. Remember it exists and start de-resuscitation as soon as their end organ dysfunction or your patient is considered resuscitated and is in the upwards trajectory and de-resuscitation is a mixed media art. Thank you all so much for being here so early this morning and we do have five minutes for questions and that was our goal.

de-resuscitation

fluid accumulation

excess fluid removal

organ dysfunction

reducing fluid administration

diuretics

ultrafiltration

individualized care