Start early so I can read to you the information I need to read to you. Welcome to session 1073, Critical Care Year Review 2. I'm Bob Heise from University of Michigan. It's a privilege to be with you. We've been programmed in this session, I think, probably eight years, which is great. Thank you for coming out, doing a veil. Let me read the information for you. The one information I do want to convey to you is, you're welcome to hang in the back, but they've told me, do not sit in the stairs, OK? We're not allowed to do that. I guess it must be a fire thing. OK, so all sessions can be evaluated through the mobile app and or the online program. Don't forget to do this when it's done, including the faculty. We're all required to disclose, as we will, our conflicts of interest, if we have them. All rights are reserved. The content is exclusive property of CHESS. You can't record it. Please assist CHESS staff by keeping the aisles clean. Claire, that's very important. That broke down a little bit in the last session. Please make room for attendees to have a seat in the middle. CME Claiming will be open on Wednesday, October 11th at noon. And I don't have any audience. Do you have any audience to respond to? No. OK, well, then put your phones away. Fair enough. So without further ado, I will present our first session here. This is an update in the acute respiratory distress syndrome, something we all think we know and love. And I'll convince you in the next 20 minutes anything about it, which is kind of sad. OK, so this is who I am. I don't have any relevant disclosures. I do write the section with Mark Segal on Corrupted Data and Mechanical Relation in the ARDS. We're going to talk about the new global definition. We'll talk about new guidelines out of the European Society, which include a lot of Americans and Canadians, just so you know, so it isn't some foreign thing. And the guidelines are worth taking a look at. We'll talk about prone ventilation echo and a little bit on bedside imaging, something that everyone's talking about personalized medicine. And the problem with that is scalability in terms of doing an RCT. And I'll get back to that later. So the biggest news for you and us is a new definition. We all start talking about Berlin this and Berlin that. Berlin is from 2012. And Berlin was a change from the past, which was a consensus, American-European consensus conference, included things like PA catheter wedge pressures, which, of course, have fallen from the face of the earth for the most part in any routine use. So Berlin was an advance, and it came up with timing a week, bilateral. I mean, everyone had, here's the one thing, what ARDS isn't is a low-bar pneumonia, OK? You've got to have bilateral disease. At least we can agree on that. In fact, some people are so confused that we're not even using that term anyway. Just saying acute hypoxemia respiratory failure, well, it's bilateral. ARDS, we don't know what. Anyway, and so instead of wedge pressures, we're saying, well, it's not an electasis, and I don't think it's heart failure, because I'm not going to prove it with a PA catheter wedge less than 19. And we're going to come up with mild, moderate, severe based on oxygenation deficit, PDF ratio, with a fudge factor for positive pressure, at least five a CPAP or PEEP. And if you read the fine print, so we all think about invasive mechanical inhalation, tube down your throat, right? But if you read the fine print, non-invasive inhalation was included in the definition. We sometimes don't remember that. And there was a hue and cry, though, to say, what about heated high flow? I mean, we had the COVID pandemic. Remember the COVID pandemic? I had a lot of people on heated high flow, hopefully not aerosolizing virus to your respiratory therapist. No, it didn't, right? We were worried about that. But we kept them off the event pretty good with the ROCS index and all that. I think they had ARDS. In fact, I would argue, instead of having some weird thing, and I think what you had a less confusing form of ARDS, and instead of confusing it with an electasis and all the other confounds we have. So what has not changed is an acute diffuse inflammatory process with predisposing risk factors. It's the same old story. Is it preceded often by sepsis being most common, medical arena trauma, perhaps being a lesser mortality inducing aversion, nosoclonal pneumonia, aspiration. So that is not any different. Timing, you get a week, which is generous, although some people said, remember the COVID double dip we experienced, particularly in the first wave, where they seemed to be getting better, and boom, more than a week out. I think they had ARDS. And then chest imaging, bilateral. So that hasn't changed. That's the same stuff. What's changed is two things, really. One is heated high flow, and the other is to say, well, we also should come up with all fairness. If you're out there in a resource limited environment, I think they get ARDS too, but you're not necessarily be able to support them with some of the things we do here in the resource lavish environments like heated high flow. So let's start with just the resource poor environment, the same PDEF under, or SF, rather, SF, saturation. The other, by the way, thing is we have a lot of saturation ratios, and that's something that we're not at present initial definition. We're, I think, hopefully, although my institution's guilty, doing fewer blood gases than we used to. But SF less than 350. Now let's go over here to the non-debated patient. PDEF less than 300, or SF less than 315, provided you're on at least 30 liters. Why? Because you get positive pressure, you get a CPAP effect. And the higher the liter flow with heated high flow, the more you get that, of at least five. And then guess what? If you're intubated, it kind of looks the same, only instead of just PDEFs, you got SFs in there to boot. So it's not that weird. It's not that weird. I will say, though, and so here's a little picture of heated high flow. So I will say, from my perspective, that I'm a little concerned about the selection of 300, but more on that in just a second. So what was the rationale? Well, look, I mean, the rationale is you want to include heated high flow. We do have some, we'll talk about ultrasound or other ways that you can look at imaging. Severity categories are important, but people are drawing about fewer and fewer ABGs. And high flow is available. So the things that we've, the practice has changed a little bit in terms of ABGs and in terms of taking an overheated high flow from the kids, right, from the pediatric environment to change our practice significantly. I think we keep a lot of, too. Oh, by the way, I'm a trialist, and we want to enroll people, we call it ARDS, who have heated high flow. So it's nice to have. Now, I worry a little bit about 300, and I got to be honest. You remember the old days pre-Berlin? We had something called acute lung injury, and that was a P to F under 300. We called ARDS under 200, and that was replaced with three steps of mild, moderate, severe Berlin with 5 CPAP. This was COVID, admittedly, but what you see here is when you shift it over from heated high flow, particularly if you're mild or moderate, to invasive ventilation, your P to F ratio, needless to say, changes. So even though you may be on heated high flow at 50 liters getting CPAP of 5, and that is the fudge factor of what was incorporated in Berlin, 5 centimeters of water, when you tube somebody, your ratio does improve. Now, who cares? Well, I mean, I care, because at least in part, when you look at LungSafe, which was an observational series in JAMA, a big international series, about 24% of patients, including a lot of Berlin severe, did not meet criteria after 24 hours. So you can say, well, does it matter? If you're on heated high flow, you're going to be lung protective because it doesn't matter. Maybe you can flip them on their belly if they're COVID. I don't know about non-COVID, but if you're on the vet, you're going to be lung protective, I hope, because that is something that's withstood this day and time. So maybe this is just me being pedantic related to being an academic person who wants to enroll trials. But I think it's a pretty liberal interpretation of what constitutes the bilateral hypoxia retrofibrosis with the risk factor. So that's what we're going to call ARDS. Are you confused yet? I mean, it sounds like a little all-embracing, particularly when you know that on lung biopsy specimens, OK, we don't biopsy the people getting better. They often don't have diffuse cellular damage. They have just pneumonia or other stuff. Or an autopsy, same thing. OK, it's a selection bias for being dead. You don't do biopsies. People are doing well, but still a little disconcerting. All right, so we have new guidelines. And again, this is the European Society of Intensive Care Medicine. They may not hit your inbox, but a very important journal. And things have changed, right? So this will synopsize a lot of information I've actually shared with you during these sessions over the last eight years. And here's a kind of synopsis that reflects those changes over time. And you see this stars. These are new things, right? So we have a new definition of ARDS. I just shared that with you. This year, but in the past, I've shared with you the hyper and hypoinflammatory phenotypes. Kel and Coffey-Berticina have found that you have a worse outcome with hyperinflammatory. So it may be ARDS, which is very heterogeneous. We should try to target trials for more specific subphenotypes. High flow nasal cannula, again, I shared that with you. Included now in the definition. It wasn't 10 years ago. Non-invasive ventilation, no comparisons. Tidal volume, hey, you know what? No change, right? Lung protective ventilation has not succumbed to what I like to call truth decay. It's still as right as it was supposed to be. Keep the plateau under 30. Go down to 4 cc per kilo if you have to. Now, we're going to study driving pressure. Canadian Practical Group is looking at that. We'll participate in that. Should you target driving pressure? I'd say you should pay attention. There's a lot of observation stuff that say keeping your driving pressure under 15 is important. And positive pressure, the issue is high versus low PEEP. And I'm always been a high PEEP kind of guy. But frankly, a lot of negative trials, you had to squint at the meta-analysis to get it to squeeze out a P value to say that a high PEEP protocol was valid. Recruitment maneuvers, there's a change, right? Remember the ARC trial? I shared with that a few years ago. The ARC trial where you had a staircase kind of big, massive lung recruitment. And then titrate that down to get to the PEEP, what happened. A lot of new authorities and CPR, those are kind of revoting. No change because we closed the books on oscillatory ventilation when the oscillate trial out of Canada had higher mortality. Prone positioning, no change. Perseva was the big article before I started presenting this to you. But I think it was 2012, I guess I want to say. Neuromuscular blockade, new recommendation. Why? Because the Pedal Network, which I was privileged to be part of, which is closing up shop this fall, had the ROSE trial. I think I shared that with you a few years ago. Did not replicate the ACQUIRESIS trial. In other words, not to say you can't give neuromuscular blockade, you just don't have to when the PDF underwent 50 people each day early on for the first 36 hours to avoid pleural pressure swings and worse lung injury. And extra-poral CO2 removal, a new recommendation based on bad literature. I mean, not bad literature, but not any benefit. Now, we used to say in a lot of these guidelines, give them a high peep. And I'm still kind of, you know, because I'll flip them prone. I mean, hey, my barriers are down on that. I grounded with Ivor Douglas at Denver Health some years ago. Man, they're prone fanatics. I think they're probably right. Obviously, not the second you tube them. Remember Perseva? 12 to 24 hours of trying to fix them. Remember what I told you about LungSafe? Maybe they're not even going to meet criteria in 24 hours. What are you flipping them prone for? They're not even there every day else anymore. You've made them better. So try to fix them first, but then flip them prone. The one thing I always had concern about, high peep versus low peep. Again, you can see how attached I am to peep. All the prone articles have always a low peep algorithm, like ARMA, like the original 6 versus 12, the original 2000. You know, no prone versus high peep. But the signal clearly is so much stronger with proning than it is with high peep. I already mentioned that to you. No prolonged recruitment maneuvers. Now, read the fine print here. That's that staircase one. You remember the Loves article, which is a high peep protocol out of Canada? They do what I like to call the ESPN, 30 for 30 recruitment maneuver, or 40 for 40. Pick them, 40 centimeters for 40 seconds. That's not the same as five minutes, starting at 50 and over 35, working your way down and fracturing alveoli. So maybe those kinds of shorter recruitment maneuvers are still permissible. But people tend to think the bad outcomes in the ARC trial were likely a result of those super aggressive ones, okay? Prone early and often. Again, I'm on board. In fact, my nursing group is creating an algorithm to try to help drive this, which is awesome, right? Because pre-COVID, you know, trying to get people prone, I mean, there was a lot of complaining going on. And I remember trying to prone the first patient we had in our RICU that we opened, our special unit, our containment unit for COVID. And I said, can I try to prone them? They literally go, you want to what? And so, but they embraced it, didn't they? And the question is, what about the truth of that? Well, there's no truth to K, but what about de-adoption? Because we had a lot of people who really came together for COVID putting people on their belly. And the question is, now that the pandemic is a little bit in the rear view mirror, I hope, are we still putting people prone? I hope so. And then no routine neuromuscular cave, the ROSE trial. It just, not to say you can't, in fact, time out, but you can't redefine print. In ProSeva, most of those patients were receiving neuromuscular cave. Now, again, Iver, God bless him. They say they can prone people at Denver Health without, let's just have to cure him. He's a better man than I am. So I have a hard time doing that. Iver's here, I think he'll be here Wednesday. So you can say, well, you kind of hedge. So flip him on there, but don't, don't your neuromuscular, okay, let's flip him on your belly, and you should. So you see what I'm saying? A little bit of a disconnect there. And then ECMO, how many people are doing ECMO at their place? Now, again, this is my old school audience response. Yeah, so big rollout since EOLIA, the most positive negative trial ever, right? Am I right on that? And then we did, I talked to you, Gallagher, about this, about Bayesian analysis. I said, God, I thought meta-analysis was weird. So anyway, I mean, again, I'm not a statistical maven, but I think ECMO's here to stay, and I'd rather put someone on ECMO than be dead, for heaven's sake. But the sickest of the sick is who they rolled in on. Now, what about, you may ask, because this is a burning question, flipping those people on their belly, okay? Observational data in need of an RCT, you ECMO people, but the basic answer is Bob Bartlett, who was at my place for many years and an ECMO pioneer, was also a prone maven. You know, the guy, he's emeritus, but he probably was doing the right thing. If you believe this observational hypothesis generating data, which should be amenable to an RCT, but, you know, I mean, you could argue with that stuff coming out of your groin, those big lines and everything. It's kind of a flaw. Well, it's a flaw to flip a severe ARDS patient, too. Isn't it all gonna get tangled up in all the tubing? So it may be the right thing to do. All right, let me finish. I don't wanna run over, say, time for my friends about imaging, and two things. Now, lung ultrasound score is something that's being advocated for you POCUS people, and it's a way to image ARDS, and I'm more of an EIT kind of guy, electrical piece tomography. I don't know, Victor, you're out here, my buddy from Mexico City, we published on that, and these are nice techniques, and this is to show you what we can do with that. We had a paper in critical care, and the problem I'm having is everyone wants to do personalized medicine, right? But I've been criticizing the APRV people for years, because they say, you gotta personalize, and you guys are doing a protocol, and you're doing it all wrong, and now I may be as guilty. I say, well, I got my little EIT machine. You know, I got a little fancy thing. How do you make that scalable for an RCT? So I know I'm starting a collaboration with Marcelo Amato. We're hopefully gonna look at this maybe on a broader scale. There has been some more bigger studies out of Canada to look at EIT, but the point I'm trying to make is that we're on a new frontier of imaging. I will say there was a Gattinoni paper the year before that tried to do a pig model to look at ultrasound and EIT, and it found some of the ultrasound issues a little disconcerting, because the higher the PEEP you go, the lung ultrasound score rather changes, and so that may not be as indicative of what's going on overall, whereas EIT seemed to track more strain, which was resulting in injury. So I'm only presenting this to you as to try to talk about some frontiers. I'm not saying go buy a machine. I'm saying that we're trying to do more for our patients on an individualized basis, right? Hyperinflammatory. Clearly, we've got this big category of acute hypoxic respiratory failure where we've liberalized a criteria called ARDS. We need to figure things out better. All right. Down here, page down. So I'll skip over this for the sake of time, but Gordon Rubefeld, Art Slutsky, and Marco Ranieri had this thing saying, you know, it's a new definition. You know, we witnessed COVID. Do we really know what we're doing? You know, ARDS is a construct. Do we really know what's going on? Maybe we're making a mountain out of, maybe we're calling stuff. We don't know really what's going on. I'll finish with saying it's a privilege to be selected for the APS Consortium. There is no new ARDSnet like Pedal, and the NIH has decided, really, that we don't know what we're doing, and what we really need to do is figure out what we're doing with a large data set of 4,000 patients. And because there's such great overlap between sepsis, ARDS, and actually pneumonia, if you look at most ARDS trials, 60% have CAP as a risk factor. So I really figure out, hone in on subgroups, and maybe the future, what we think, is in personalizing our approach based on some of these subphenotypes that we hopefully identify beyond the inflammatory, hypoinflammatory thing. So what have I told you real quick? New definitions include heated high flow, and a lot of S-to-F stuff. It talks about resource-limited environments. European guidelines do advocate for NIV, but I say, if you're gonna advocate for NIV, you should make it a helmet, no one uses it, because I just asked the last group, and no one raised their hand. Ultrasound EIT images, techniques which are not ready for primetime, they're not really scalable, but if we get some data one day, maybe we'll have some scalable thing. And let me leave you with a quote, because a guide for the perplexed, such as me, now with ARDS, from Karl Popper, every solution to a problem, like the new criteria for ARDS, raises new unsolved problems, so thank you. All right, great, Angel Cas, from Cleveland Clinic, I got it right this time, to tell us about sepsis, a repeat offender from last year. That's correct, thank you, Bob, and thank you for all of you for being here, and thanks, Bob, for putting this really great set of sessions for the last 10 years, and this is the second year I'm doing it, I inherited it from my good friend and mentor, Steve Simpson, who is sitting here in the front, so if you don't like how I do, just get him back next year, just write in the comments, get out of here. So, I'll be talking about sepsis a year in review, I have no relevant disclosures, I was a member of the 2021 Surviving Sepsis Panel, and I will go over a little bit about the CDC recommendations, antibiotics, fluids, and then some data on steroids for community-acquired pneumonia. And this is, I think, a very, very important piece of data, it was published by the CDC a few months ago, and it highlights a few things, it was a survey of over 5,000 hospitals in the US, and it had a really high rate of response, over 90%, and what they asked was to the different hospitals about four domains, whether if they had a sepsis program, two, if they had programs to identify sepsis more expeditiously, if they had management protocols, and fourth, which is something really eye-opening, whether there was leadership support for the people in charge of sepsis in the local hospitals. And here on the right, as you can see, most of the hospitals that treat sepsis in our country are smaller hospitals, you can see 30% are hospitals that are 25 beds or less, and if we do the math, it's around almost 50% of hospitals that are less than 100 beds. So really, really important stuff, because we all think about the well-resourced environments that are big hospitals, but in reality, most of sepsis is taken care of in smaller hospitals. And why is that particularly important? It's because, as you can see here, the smaller hospitals typically struggle more in having a committee that would take care of, manage, steer in sepsis care in the hospitals, or having identification strategies, or having protocols that would help in the homogenization of the management of sepsis with antibiotics and fluids. I mean, it gets better as the hospitals tend to get larger in size, but what I think, there's still room for improvement is in the leadership support, because even the hospitals that are 500 or larger, the person who is in charge of the sepsis program, only 80% of those have a protected time to actually do the job that it takes. If some of you actually are in charge of doing this, you know that it's almost a full-time job to trying to steer, do the right thing to try to get the whole hospitals to do sepsis care in a homogeneous way. Not only that, as you can see here, there is no allocating of resources, because data analysis is really important, IT support is really important, and that is also lacking, especially in the hospitals that are smaller size. And then there's also not much opportunity to have face time with the executives, with the people that actually make the decisions when it comes to the financial decision making. So really eye-opening, and what the CDC has proposed is that core elements for any sepsis program, and it has to have hospital leadership commitment, meaning there has to be protected time for the person in charge of the sepsis program. It has to be accountability, meaning somebody in charge of that program. It has to have multi-professional expertise, meaning physicians from different disciplines and also nursing, pharmacy, et cetera, to be able to have a well-rounded view of the management of sepsis in that specific hospital. Action, meaning there has to be strategies implemented, and those strategies need to be tracked, and then reported, and more important is education, because that is the only way that you close a loop and make sure that the areas that need to be improved are actually improved. Now going to antibiotics and source control. I think we all know that there are certain times of the day that maybe we suspect that sepsis care may not be as good as other times, and this is an interesting study that actually looked at around 1,600 patients with hospital-onset sepsis, so patients who were hospitalized were not admitted for sepsis and developed hospital sepsis in the ward. They used the definition of the CDC, meaning that when blood cultures were drawn, they looked 48 hours before and after, and if there was administration of antibiotics and endocrine damage, that's how the patient met the criteria for sepsis. The majority of those cases occurred in the medicine wards, 82%. Average time for the onset of sepsis was about seven days. Sepsis-to-antibiotic time is about four hours, which is, one can argue, yeah, it's not great, but it's not too bad either. However, when you look at day shift and night shift, you can see that there is a significant increase in delay of antibiotic administration at night, and I think this graph says it all. At night is bad, but these times of transition, when people are trying to get out of the hospital or there is the sign-out, that is when it's probably the worst time to develop sepsis. So it seems like if at this time you develop sepsis, you're kind of better off going to the ER, signing yourself out AMA. But what I'm trying to say here is this is something that could be helped if we have pathways in process that would streamline that care and not rely on so much on the manual management of sepsis. If there is a process, a protocol that would automate all of this would be a lot easier. Also something that is very dear to my heart, that we, if you have seen the previous session with Brian Wayne, that he says everybody gets vancosing, and that is not so far from the truth, right? And we need to, I think, be more cognizant about the antibiotics we're given, but also being stewards of stopping those antibiotics as soon as we don't think we need them, and de-escalate, because just as it is important to give antibiotics early, it's just as important to de-escalate as soon as possible. This is a study that looked at over 35,000 patients in over 300 hospitals, and what they looked at is what happens if we use this combination, vancosing, vancomyopen, or vancifepine, and the outcome was AKI, stage two or three. And those patients were propensity score matched, and as you can see here, the patients that received here in red, vancomycin and zosyn, when compared to vancomycin and meropenem, had a higher likelihood of developing AKI, especially those who had a GFR more than 60. And when this was looked at 48 hours, those patients who had remained on this combination of antibiotics had a three times chance of developing AKI. So does that mean we need to switch to vancomycin and meropenem to everyone, and just not do vancosing but vancomyopenem? No, what that means is two things. One, we need to give antibiotics early, but that doesn't mean that every patient gets the same cocktail of antibiotics, which seems to be something in a shift of practice. But two is that we need to reassess every day for the need of the antibiotics we're giving, because if we keep them for longer, the risk of side effects and of damage produced by those antibiotics, it becomes bigger. Now, going to source control, and this is something that we're never gonna have a randomized control trial, and being part of the last surviving sepsis guidelines, you can see that a lot of the recommendations are low quality of evidence, but that is just because we're never going to have, for example, a randomized control trial that's gonna evaluate antibiotics versus no antibiotics. That could not be done. Therefore, you start with observational data. The best you start with is a low quality of evidence, and it's really rare that it will go up from there. So this study looked at source control, whether it happened early, before six hours, or late, past six hours, and the primary outcome was mortality at 90 days. As you can see here, hospitals that had surgeon availability in-house 24 hours were more likely to achieve source control early. If the hospital did not have mandated surgeon in-house, were more likely to produce late. Time to antibiotics was similar. Time to source control was vastly different, and that was the purpose of the study. But what we can see is that certain locations, like GI or abdominal, were more likely to receive intervention early, as opposed to, for example, orthopedic and cranial, or pancreatic biliary, which tends to happen a lot later. But why is this important? So the adjusted odds ratio for survival, for mortality, is .71 if we do source control in the first six hours. And when this was quantified for every hour of delay in source control, we are potentially increasing mortality by one to 2%. So something really important, because a lot of times it takes a lot of effort to get our colleagues in the interventional suites, either IR, et cetera, whoever needs to do the procedure to accomplish source control, this is something really important. I don't know that we're gonna have better evidence as far as a randomized control trial, randomizing patients to early or late source control. And this is some of the areas in which we're gonna have to rely on retrospective data. Now fluids. In fluids, we have had a rollercoaster. We used to be very aggressive with fluids. The patients don't get well until they swell, and now we don't, we like to give 500 milliliters and walk away from the patient. And I don't think that either approach is correct. Probably something more in the middle is, and I'm gonna try to show you this in the next few slides. First we have Clovers. This was a study that was published last year. It was an unblinded superiority randomized control trial that evaluated a restrictive versus a liberal strategy, and those patients were randomized within the first four hours of sepsis onset, and they had received one to three liters, and the primary outcome was 90-day mortality. Here's a little bit of a glance of the program. I'm not gonna go too much in detail, but the restrictive group, if they were hypotensive after one to three liters, all fluids and boluses and maintenance were stopped, and then the patient could receive up to two liters. In the liberal approach, then they stopped all the maintenance, but they could get additional fluids. If they remain hypotensive, you can see here, the restrictive approach favor an early vasopressor intervention, as opposed to the liberal approach in which those patients would get additional boluses as long as there was some hemodynamic response. And then rescue strategies where if the patient in the restrictive group had any of these parameters, like severe hypotension with a MAP less than 50, or refractory hypotension on 20 mics of norepinephrine, lacked a level more than four, et cetera, the patient could get fluids in the restrictive approach. In the liberal approach, this was a time in which the patient could get vasopressors. And I could literally paste the Kaplan-Meier from any trial in the last few years, and you would not be able to tell whether it was from this trial or not, because basically, all the trials showed no mortality or survival benefit. But I think what is important, and this is something that I want to drive home, is that these patients here, before they were randomized, got an average two liters. So the strategy in which we are advocating for a restrictive approach of fluids, we need to be careful with what we call restrictive approach. And the previous 2020-2021 recommendation from Surviving Sepsis, that panel was unable to make a recommendation, because there was so much heterogeneity in between what was called restrictive versus liberal. And I'm going to show you some of that in the next few slides. Then a meta-analysis tried to put all of this together, included 13 trials. Eight of those studies had low risk of bias. And then six of them look at adverse effects. And again, I could pull any forest plot from any. They all look the same. There is no difference in mortality, no difference in adverse effects. But I think we need to take a little bit of a deeper dive into this. This is a table that actually we used to compare all the trials. And at the time when the guidelines were made in 2021, the classic had only the pilot study that was published in 2016. The classic study that came last year was released after the guidelines came up. But as you can see, classic and Clover's are the ones that have the highest patient enrollment, over 1,500. But then all the other trials, prior to that, had a very small number of patients. Inclusion criteria were so different, meaning some of these studies require the 30 mLs per kilogram. Some of them require absolutely no bolus at all. The duration was also important. Some of them look at patients only for six hours. Some of them look at patients for up to five days. So looking at different interventions in the ICU is very different if the duration is totally different. And then what I think was the most salient comparison was that what some of the studies called liberal, it resembled a lot to what the other study had called restrictive. So to advocate for a liberal or a restrictive approach without knowing exactly what a restrictive approach is, I think is dangerous. And I think one thing that we should stay away from is from being shy from giving fluids. The 30 mLs per kilogram is a good start for most patients. That doesn't mean that every patient should get 30 mLs per kilogram, but it doesn't mean that we should be giving 500 milliliters and walk away either, because that's also something that we're seeing more and more. And then the classic study look at patients up to one year. And again, there was no difference in outcomes and no difference in quality of life. And I like to present this slide because this slide includes the biggest randomized controlled trials in sepsis up to date in sepsis resuscitation. The RIVERS trial, PROCESS, ARISE, PROMIS, CLASSIC, and CLOVERS. And what you see there in green is the amount of fluids that the patient received before being randomized in the study. So even the studies that are evaluating, are we gonna give a little bit of fluids or maybe a little bit more? Before they tested that hypothesis, those patients on average received two liters. The only difference here is in CLASSIC, that was the amount that they received in the previous 24 hours, not prior to enrollment. But as you can see, it's somewhat in the neighborhood of two or two and a half liters, which is where the 30 mLs per kilogram came from. There's never going to be a randomized controlled trial looking at 30 versus 25 or 30 versus 26. This is unfortunately the best data that I think it's going to have. But again, this is where the clinician at the bedside cannot be replaced. You need to reassess your patient and assess the need for further fluids. Going to obstetric sepsis, we had two trials that look at that. One of them was the use of intrapartum acitromycin versus placebo, looking at neonatal death. Over 12,000 patients, two grams of acitromycin prior to labor or during labor, I'm sorry. And the endpoint was neonatal sepsis or mortality. They also look at neonatal infections and the need for antibiotics. And as you can see here, there was no difference between the composite endpoint or either independently. One thing that was noticed was that maybe the newborns in these cases had less infections or less antibiotic use. And then when they look at the maternal effect, you can see that maybe there was a little bit less of mastitis or infection or fever. And this is the signal that I think gets confirmed in the other study, which is this one. It was published in the New England earlier this year as well. This was a study that was done in several countries in three different continents, Africa, Asian, Latin American, include almost 30,000 patients. And again, the intervention was the same, two grams of acitromycin in patients who had planned vaginal birth. But they look at two outcomes, look at maternal sepsis or death and look at neonatal sepsis or death. And as you can see here, there was actually a difference in maternal sepsis or death, not so much, just like the other study in neonatal outcomes. So what we can get out of these studies is that probably, and this is mostly done in areas, environments that are low resource, that the use of intrapartum acitromycin can prevent maternal deaths. And something that is really important because sepsis is one of the important causes of mortality around labor and delivery. Last, I'm gonna talk about steroids in severe pneumonia. And it's not uncommon that we have one trial that says one thing and sometimes in the next issue of the same journal, a trial that says exactly the opposite. So this is something that we have, first of all, guidelines that were published earlier this year from the different societies in Europe and ALAT that look at whether we should be using corticosteroids in severe community-acquired pneumonia. And what the guidelines recommended, which is in synchrony what the ATS guidelines recommended six years ago, is that the suggestion was to not use steroids unless the patients were in shock. As you can see here, there was a conditional recommendation with low quality of evidence. And you see of the forest plots that inform this guideline, there was some benefit in ICU mortality, but when you look at hospital mortality, there was no difference. And the study that has the most weight in this guideline was the Midouri study, which was published last year. And I want to show you some of the details of this study and the Cape Cod study and trying to compare, contrast some of the differences and maybe where we can make our own conclusions. So this is the Midouri study. There was a double-blind randomized controlled trial, enrolled 600 patients. However, the initial plan was to enroll 1,400. But as Bob mentioned, if you remember what happened a few years ago, COVID came and threw everything down the window. This was a study that was done at the VA center. And if you work at a VA, you know that your population is vastly males. There is a very small fraction of females in this study. And the patients were admitted if they had severe CAP or H-CAP. That definition no longer exists. And they could be included all the way up to 96 hours. So again, if you remember something, all of the sepsis trials, the early intervention is what is key. And this is something that the study maybe enrolled patients a little bit too far out. The stator of choice was methylprednisolone, 40 milligrams per day for seven days, and then a 20-day taper. And the primary endpoint was 60-day mortality. Again, I can show you graphs from any other trials. There was no difference in survival, either in the patients overall, or those who were on mechanical ventilation, or those who were not on mechanical ventilation. And then we have the Cape Cod study, the study that came early a few months ago. It was a multicenter randomized controlled trial, double-blind, enrolled 800 patients. It included patients in the ICU with severe CAP. The stator of choice in this case was hydrocortisone for four to eight days, and then followed by a taper of eight to 14 days. And the primary outcome was eight to 14, I'm sorry, 28-day mortality. Again, here you see that there is a benefit towards hydrocortisone, and also lower need for mechanical ventilation, and lower use of vasopressors in those patients who receive hydrocortisone. And when we look at a subgroup analysis that were predefined, we see that females actually benefit more than male. I couldn't find the information whether this was adjusted for multiple comparison, but something that I think it's important to contrast, because the study that showed no benefit, 96% of the patients were males. When they look at the adverse effects, we have hospital-acquiring infection and GI bleat. You were no different in this group that received steroids, but those patients actually required a little bit more insulin during their hospital stay. So now let's compare them to both studies and see what conclusions we can make out of them. First, the sample size in the Midouri study was only 500, which was way short of what was initially planned to be enrolled. The gender composition of the population was really important, I think. 96% in the Midouri study were males, as opposed to 69% in the Cape Cod. The inclusion criteria were also different. The inclusion criteria in the Midouri study was the old ATS IDSA definition of severe pneumonia, which includes either one of these major criteria, mechanical ventilation or septic shock, or three of the minor that you can see there. Cape Cod had more parameters that were along the lines of hypoxemia. Mechanical ventilation with a P more than five, high flow, or non-rebreather with a PF ratio less than 300. Also included patients with a pneumonia severity index of one more than 130, which is a group five. Also what there is a difference is the initiation of the treatment. These patients received initiation all the way to 96 hours, although most of them received in the first 48 hours. Cape Cod was early, first 24 hours. So I think that's also where some of the difference could be. Some could argue that maybe it's a difference in the type of steroid. I mean, those doses are equivalent. It's kind of hard to make the argument that one of these was better than the other. When it comes to the severity of illness, we see that in the group four and group five of the pneumonia severity index, they're pretty close. I don't know that that explains. But what I think that it's important is in H, there were a lot of patients with H cap in the Miduri group, meaning there were patients who came from nursing homes, from extended care facilities, who had been recently hospitalized or had received IV antibiotics or IV therapy recently, as opposed to Cape Cod, which was, for the most part, pure community-acquired pneumonia. And that is demonstrated in the different pathogens. You can see that of the most commonly recovered pathogens was strep pneumo, which goes along the lines of community-acquired pneumonia, as opposed to in the Miduri study that included Pseudomonas staph aureus, which looks more like a hospital type of environment. So how do we reconcile these studies? I mean, there's probably not gonna be a guideline for another couple of years in this, but if we have a patient who has severe community-acquired pneumonia, doesn't meet the criteria of the healthcare associated that used to be a definition, and that has parameters that meet the hypoxemia requirements, I think they should probably receive steroids. But again, we're not gonna have guidelines on this for a little while. So just to recap, not bank sourcing for everyone. We need to tailor the antibiotics and stop them early. If you run a sepsis program, you can use this document to try to get support for what you're doing. It is a lot of work, and it's really important. And especially coming 2024, it's gonna be part of the CMS value-based performance. Going to fluids. We cannot advocate for restrictive if we don't know what exactly it is. I think that the 30 mLs per kilogram is a good start for most patients, and then we need to tailor and individualize the additional amount of fluids that our patients need. For maternal sepsis, azithromycin seems to decrease maternal, improve maternal outcomes. And then last, potentially, I think there could be a role for hydrocortisone in the management of patients with severe community-acquired pneumonia. Thank you. Great, thank you, Angel. Our last speaker, MJ Reed from Geisinger Clinic. We're especially pleased to have her rally to make it. She almost didn't make the trip, so we're pleased that she's able to present on surgical critical care again this year. Thank you. Thank you, Bob. And then the one thing that Angel did not say was the fact that make sure that you wake your surgical colleagues up for source control, and tell them that it changes mortality to get their butts out of bed. Of interest, how many of my surgical tribe is here today? Surgical intensivists, raise your hand. Oh, boy. All right. That's why you're our speaker. That's right, that's why. So I can cast some shade on some of my subspecialists. All right. So surgical critical care and review. Basically, I am, as Bob said, I'm a multidisciplinary intensivist and a trauma surgeon and surgical intensivist, and I do ECMO as well. I have no disclosures, but please feel free to contact me at my email. I am what they call a vintage surgeon. I have seen, I've been around a lot, like we all have. And- We're looking at that quote. I was looking at it. So we're going to talk a little bit about some prognostics. When I look at these, I try to make sure that everyone can use them a little bit from the surgical intensive care world. We're going to look at an adjusted SOFA score for prognostication of emergency EGS patients. I'm going to present the metric trial on aspirin versus low molecular weight heparin, discuss pre-hospital, the patch trial, and then we're going to evaluate adrenergic blockade and severe traumatic brain injury. So the performance of acute SOFA score for prognostication in emergency surgical patients has not been studied. And it would be very helpful if we had that. It would be very helpful for those in the audience, as well as the surgeons on the other side, to be able to identify patients who we know are going to do worse, and we know need to be triaged to at least intermediate care, if not critical care. There's a paper here that I did not review that I have a reference to that shows that we under-triage almost 12% of patients, and that leads to increased morbidity and mortality. So we need to do better. Perhaps this is helpful. This was a retrospective cohort study in adult patients over a two-year period at a single center looking at abdominal emergency general surgery. The primary outcome was mortality. The results were 578 patients undergoing abdominal emergency surgery, and the in-hospital mortality there was 4.8. Independent predictors for mortality in their study were mesenteric ischemia, gastrointestinal perforation, age of 65 or older, and increasing QSOFA score. So they proposed a modified QSOFA score, and their conclusion was, based on what their findings were, that there should be a pro-spectrum randomized validation of this score. But let's go over it. The other variables that were interesting here was not only mortality, but it was also the need for ICU care postoperatively, or even preoperatively, and the need for mechanical ventilation, which oftentimes can be missed. Secondary goal was to increase the power of the QSOFA score, and they did that by adding a few more variables. So this is a busy slide, but let's look. So the age of greater than 65 years, as you can see here, was significant. MI here does not mean myocardial infarction. It means mesenteric ischemia, and mesenteric ischemia is a bad actor. And oftentimes, mesenteric ischemia, because there's no inflow and there's no outflow, does not have a high lactate, just for those who still believe in high lactate for ischemic bowel. GI perforation was also a problem, but it was mostly colonic perforation, as well as a GCS score of less than 14, and of course, an increase in QSOFA score. So what does that mean put all together? So calculation of their quad SOFA score just like a QSOFA score, if you had a systolic less than 100, you got a point, respiratory, Glasgow Coma score. You added the age, but really look here. Gastrointestinal perforation gave you one, but mesenteric ischemia, which oftentimes we can diagnose on a high-resolution CT scan preoperatively, gives you three. And as you can see here, the quad SOFA score actually is more of a linear type of relationship rather than that parabolic one of QSOFA score, excuse me, and increases the ability to perhaps identify those patients who need perioperative ICU level of care. And again, here are the variables, the secondary variables. We have ICU. Again, the mesenteric ischemia is a bad actor as well as when it comes to ventilation. So the limitation of this study, although it's a small study, it did not include frailty, which is becoming more and more significant in our surgical patients. It was retrospective and all that entails including bias. It's a single center study and we have not validated the quad SOFA score in other EGS type of patients. So it needs validation, but it's an interesting score and I think it's something that hopefully will help develop to help our multidisciplinary colleagues. Okay, this is the metric style and I've spread some shade on my orthopedic colleagues for so long about this that I thought I should actually present it. So this is looking at a aspirin versus low molecular weight thromboprophylaxis after fractures in trauma patients. It's a multi-center randomized non-inferior trial, 18 years of age or older on those patients who had at least one extremity fracture and or acetabular pelvic fracture, which as you all know, has a higher incidence of co-trauma injuries. Patients were randomly assigned to receive low molecular weight heparin at a dose of 30 BID or daily dose of aspirin of 81 milligrams. After hospital discharge, the patients continue thromboprophylaxis according to their clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcome was non-fatal pulmonary embolism, deep vein thrombosis and bleeding complications. Now as a multidisciplinary intensivist, you understand why for several years I have had dubious thoughts on this. But however, it was 12,000 patients were randomly assigned. That's a pretty good number. The mean age was 44. 7% of them had previous venous thromboembolism. Almost 3% had cancer. And death occurred in the same, in both groups. And deep vein thrombosis was a little bit higher in the aspirin group. But here's death. So the initial primary outcome was death by pulmonary embolism. And then during the course of the study, they changed it to death by all comers. And as you can see here, there is possible PE-related deaths that is a little bit higher in the aspirin group, low molecular weight. But overall, there was no real significant difference. Now, when you delve into it, there's a little bit of caveats here. One of them, and I hope that this actually shows up, is the injury severity score. Okay, so injury severity score of these patients, almost half of them were relatively minor injuries. Okay, so they didn't have a lot of comorbidities. But they did have a good number that were moderate injuries. Okay, so people that you may actually have ICU, in your ICUs. And then a significant number, almost 12% that had severe trauma. So the safety was good, as you could imagine. Bleeding complications were the same. There were an increased venous thrombosis, but it wasn't statistically significant. So the limitations of this, they had anticipated problems with enrollment. So they were allowed to receive up to two doses of low molecular weight heparin prior to being enrolled, which, based on your GFR, may actually last a little bit longer than you think it does. The duration of thromboprophylaxis in the hospital and discharge were not mandated. And owing to the trial's open-end design, secondary outcomes could have been biased. And the primary outcome was changed from death by pulmonary embolism, which we're all really kind of interested in, to death by any cause. So I feel less guilty now. Now, the PATCH trial. We've heard a lot about trans-enzymic acid through the CRASH-2, CRASH-3, the HALTED trial for GI bleeding. So does it help when patients are identified as high-risk bleeders, high-risk trauma patients in the field? So again, it was a multinational double-blinded trial, randomized, well done. And it was for patients who were at high risk for coagulopathy. So remember, we try to avoid the triangle of death, right? So acidosis, hypocoagulability, and hypothermia. So in the treatment group, they got a gram of trans-enzymic acid within three hours of their injury in the field. And then again, once they arrived at a tertiary trauma facility. Placebo, they received nothing. So survivable with favorable outcomes was the same. It did not change. There was not vascular occlusive disease events that were really changed. So the conclusion was among adults who are high risk, giving in the field trans-enzymic acid does not make a difference. The limitations, however, are this. About 13% of the patients were lost to follow-up. Some patients did not receive all the trans-enzymic acid, or they went ahead and received trans-enzymic acid out of the study. The trial involved patients with severe injuries who were high risk, but they also came to places that were level three, or level one tertiary care trauma centers. And so that makes a difference because if you have the resources, you're taking these patients to a resource-rich environment, okay, it may not make a difference. But if you're in that, one of those small 100-bed hospitals in the middle of Iowa or the middle of South Dakota, you may need that trans-enzymic acid. So I don't think we have that question answered as of yet. Okay, so those of us who take care of severe traumatic brain injury know that there's that hyperadrenal, tachycardia, tachypnea, hypertension, things like that. And we oftentimes treat it with anti-adrenergic, clonopine, propranolol, beta blockers. So this is a phase two small trial. It's not out yet. We need a larger trial. But it was the effect of propranolol and clonidine after severe trauma, looking at its effect on mortality and ventilator-free days. So patients received a placebo or the propranolol plus the clonidine for seven days. The primary outcome was ventilator-free days at 28 days. The secondary outcome included catecholamine levels, hospital length of stay, which is important, mortality, and long-term functional status. And they had a planned futility assessment at mid-study. Unfortunately, everybody was compliant. There were no patient experienced any cardiac dysrhythmias or cardiac arrest. However, because of no difference, because of futility, it was stopped early. There was no significant difference in ventilator-free days between the treatment and control groups. And other than the fact that the symptoms of tachycardia and hypertension were better, it did not make an effect either on the primary outcome or the secondary outcome. So despite its safety, and most of us actually will do this, there's no real good evidence that it changes outcomes. So we do need perhaps a multicenter prospective trial to make sure that what we're doing in clinical practice is something that we should be doing. All right, now this was not one of our goals, but I thought it was something that as a vintage surgeon, I need to just at least bring up. There was an article in the British Journal of Surgery that was a survey of the UK surgical residents and workforce members, both male and female. And 1,700 people participated in the survey with 51% of women. It showed that almost 64% of those that answered were reported being targets of sexual harassment versus 23% of men. And let me just say, 23% were men. Additionally, 30% of women had been sexually assaulted versus 7% of men. And of that, almost 1% reported being raped. And then evaluations of the organizations that handled these, and this is in Britain in the national health system, that it looked like, according to the respondents, that the women did not get, felt that their concerns were not heard versus the males. Now, I bring this up not because it's going to change your clinical practice, but I bring this up because after 35 years as a surgeon, that when we have almost 50% of our surgical residents and fellows are females, and almost 50% of our attendings are females, I'm concerned that this is still a problem. And I don't have the answers, and I hope that over the course of the next decades that we do, this is past the Me Too movement, this is past when I graduated, it was 5% women. So I'm hoping, and I bring this to your attention, because hopefully we'll be able to make a change in this soon, if we haven't already, but it is still a problem, or at least it is registered as a problem. Okay, sorry about that. So, well, I'm not sorry about that, actually. So some of the things I wanted articles to consider here is a good one, that's the under-triage one, and that's the one that most of us, because we do ICU triage, need to be aware of. And then, again, this is something that, it seems like rib stabilization is an operation that's looking for an indication, but it seems to be a trend, maybe, of helping, especially for those patients after CPR, things like that, right, that maybe that will be helpful for ventilator-free days. So those are things to keep an eye out for. These are my references. And once again, thank you again for inviting me. Don't forget to set up your sessions. And have happy trails and safe sailing, okay? Thank you.

surgical critical care

adjusted SOFA score

mortality risk

metric trial

thromboprophylaxis

fractures

propranolol

clonidine

sexual harassment