So, all right, so I'm going to be talking about peritransplant and GI considerations. This is going to be quick. I don't think we have a lot of time. But the full length of the guidelines is, you know, easily found online and all of our methodology as well as, you know, what went into our decision making is all very transparent and found, you know, in the supplement to our guidelines. So I have no relevant disclosures. A shout out to all of the authors and especially our vice chairs, Dean and Waleed, you know, who were instrumental in sort of, you know, helping us complete the guidelines and getting them published. So a brief overview of methodology. All of the questions were in PICO format. There was a systematic review of the literature for every question. You know, for every included study, we did a risk of bias assessment, then used meta-analytic techniques to summarize the evidence, and we used the great methodology to guide both the assessment of our quality of evidence and the strength of our recommendations. And again, our recommendations are either strong or conditional, and when they're strong, we say we recommend, and when they're conditional, we say we suggest. Okay, so moving on to the GI considerations, our first PICO question was, should we, in people who have acute and chronic liver failure, should we recommend performing endoscopy with no later than 12 hours of presentation, and we recommended that performing endoscopy no later than 12 hours of presentation in critically ill patients with ACLF and portal hypertensive bleeding. This was actually a best practice statement, and the reason it was a best practice statement was because there was no prospective data, but, you know, when we looked at physiological considerations, and especially that ACLF itself is sometimes triggered by GI bleeding, we thought that endoscopy would lead to faster cessation of the bleeding source, prevent hemodynamic instability and other complications, and so the panel voted strongly to recommend early endoscopy, and that is within 12 hours of presentation. Our next PICO question pertained to the use of proton pump inhibitors in portal hypertensive bleeding, and again, this was, so, you know, our guidelines had very few strong recommendations, so these are some of the questions that we actually, you know, strongly recommended based on the evidence or the decision-making of the panel, and so in the case of proton pump inhibitors, we recommended using proton pump inhibitors in critically ill acute and chronic liver failure patients with portal hypertensive bleeding, and this was a very strong recommendation. However, there was low quality of evidence, and the reason there was low quality of evidence was that, you know, there was no direct, there was not very much direct evidence in people with ACLF, but there were three meta-analyses that found that the use of EPIs in portal hypertensive bleeding reduces the risk of re-bleeding, but really did not have very much of an impact on mortality, and we downgraded the level of evidence because the inclusion of retrospective, because of the inclusion of retrospective studies in all of these meta-analyses, and the high risk of bias from non-standardized inclusion and treatment criteria, but when we extrapolated evidence from the non-vericeal cohorts, we issued a strong recommendation for, you know, for the speaker question. The next speaker question was the use of octreotide or somatostatin analogs in portal hypertensive bleeding, and we recommended that, we strongly recommended using octreotide or somatostatin analogs for treatment of portal hypertensive bleeding in critically ill patients with acute and chronic liver failure. This was a strong recommendation, and there was moderate quality of evidence, and based on our systematic review of prospective trials, we found that the use of somatostatin analogs was actually associated with a substantially lower risk of mortality, and, you know, when we calculated it out, it was 30 fewer deaths per 1,000 patients. The next speaker question was, you know, was pertained to the use of TIPS, or transjugular intrahepatic portosystemic shunt placement, in patients in critically ill acute and chronic liver failure patients with recurrent vericeal bleeding, and here we suggested, which is now again, this is a conditional recommendation with low quality of evidence, we suggested the use of transjugular intrahepatic portosystemic shunt for recurrent vericeal bleeding after medical and endoscopic intervention, but, you know, over continued endoscopic therapy. But however, we qualified this recommendation saying that, you know, TIPS requires appropriate screening, and this intervention also requires access to an experienced operator at a center with expertise, and our rationale was that, you know, TIPS was associated with significant decreases of mortality and bleeding rates at one year, however, it also causes hepatic encephalopathy, and so in patients with, you know, significant hepatic encephalopathy, it should be considered on a case-by-case basis. Our final PICO question in the GI subsection was whether we should recommend large volume paracentesis in critically ill patients with ACLF and TEN societies, and we, and this was again a best practice statement, and we did recommend performing large volume paracentesis with measurement of intra-abdominal pressure in critically ill patients with ACLF with TEN societies, and intra-abdominal hypertension or hemodynamic renal or respiratory compromise. And again, the rationale for this, you know, the reason it was a best practice statement was that, you know, we could not find any randomized or prospective data to guide our recommendations. However, when you look, again, you know, there was a strong, very strong physiological rationale, you know, there are obviously draining societies, especially TEN societies and critically ill patients, and especially in people who have intra-abdominal hypertension lowers the intra-abdominal pressure, and in heterogeneous critically ill patients, relief of intra-abdominal hypertension is associated with improved organ function. Okay. Moving on to peritransplant considerations, the, our first speaker question was, in diseased liver graft donors, should we recommend administration of corticosteroids? Again, conditional recommendation, very low quality of evidence, we suggested using systemic steroids for diseased liver graft donors, and the rationale for this was that if you look at brain dead donors, results from pooled RCTs demonstrated, you know, about a 5% absolute risk reduction of liver graft dysfunction in those receiving corticosteroids. Our next speaker question pertained to the use of balanced crystalloid solutions perioperatively in liver transplant recipients, and we suggested the use of balanced or normal chloramic crystalloid solutions over hyperchloramic saline for peritransplant liver, fluid liver, for peritransplant fluid replacement in liver transplant recipients, again, conditional recommendation, low quality of evidence. There was nothing that actually, there was no direct evidence in liver transplant recipients, but in heterogeneous critically ill patients, you know, there is possibly a reduction in mortality and major adverse kidney events with the use of balanced solutions. The next speaker question pertained to the use of albumin in the intraoperative period, and again, we suggested the use of albumin over crystalloid for intraoperative volume replacement. Again, this was a conditional recommendation, and there was, you know, pretty low quality of evidence. Again, no direct evidence for liver transplantation, but, you know, again, using indirect evidence, we found that albumin may be beneficial. Our final PICO question that we actually issued a recommendation for was pertained to the use of extracorporeal liver support, and, you know, probably the most controversial recommendation, so we suggested using, either using extracorporeal liver support or standard medical therapy in critically ill ALF or ACLF patients, and this was a conditional recommendation, very low quality of evidence. We qualified the statement saying, you know, providers may choose to use artificial liver support based on local availability, familiarity with its use, and available resources, and the rationale for this was that if you look at pool data, you know, from about 24 randomized controlled trials, and if you look at ACLF and ALF together, there is a small mortality benefit, but if you analyze them separately, you know, neither is statistically significant, and, you know, these therapies require expertise, you have limited access, and there is a high cost, and so, you know, so they should only be used in the, you know, hands of people who sort of know how to use them and are familiar with their use and have expertise. There were a few questions in the perioperative group that we, there was insufficient evidence to issue a recommendation, and the, those questions were the use of the donor risk index in liver allografts, the choice of intraoperative hemodynamic monitoring, the use of peritransplant fluid restrictions with vasopressors, and early extubation. So we just couldn't issue a recommendation because we could find absolutely no evidence pertaining to these questions. So that is it for both the GI and peritransplant recommendations. I will now hand this over to my co-chair, Ram, who's going to talk about neurology and ID recommendations. DR. RAM RAMACHANDRAN. Good morning. So I'll cover neurologic and ID in the next section. All right, so no disclosures, again, just a acknowledgement of the great work done by the group. So let's talk about neurologic considerations in ALF and ACLF. So the first question is utility of invasive intracranial monitoring in acute liver failure. And so the recommendation here is that we suggest not using invasive ISP monitoring for critically ill ALF patients with advanced grade encephalopathy. This is, again, a conditional recommendation with low quality of evidence. And the rationale is that the observational studies in this field so far have not demonstrated a mortality benefit. There's no RCTs. And also, from a safety standpoint, there are safety concerns regarding bleeding and infection risk, especially with the subdural and the intraparenchymal devices. Moving on to sort of the second question is application of extracorporeal therapy in acute liver failure. And here we suggest, when available, using plasma exchange with FFP in critically ill ALF patients who develop hyperammonemia defined as a serum ammonia greater than 150. Again, conditional recommendation, low quality of evidence. And the rationale here is there is RCT-level data, a single RCT, that demonstrate a transplant-free survival benefit using high-volume plasma exchange defined as 8 to 12 liters of FFP. And there's also newer data for standard plasma exchange with the same efficacy compared to standard of care. And the potential mechanism of action of plasma exchange in ALF is that it mitigates the systemic cytokine surge due to acute hepatic failure and thereby improves systemic hemodynamics, which then translates to improved mortality. And then one thing, just as an acknowledgment, I think this may become more important in the next iteration of the liver failure guidelines is the growing role of high-dose CRRT defined as 60 to 90 mils per kilogram per hour of dialysate in the management of hyperammonemia. Again, defined as greater than 150. And there is growing evidence of its utility and its benefit both from a neurologic standpoint from a transplant-free survival benefit. So I just wanted to highlight the concept of high-dose CRRT in this context. Moving on to therapies to decrease ICP in ALF, talking about hypertonic saline. In this recommendation, we suggest using hypertonic saline in critically ill ALF patients who are at risk for developing intracranial hypertension, again, conditional recommendation based on low-quality evidence. And the risk factors for intracranial hypertension is hyperammonemia defined as greater than 150, high-grade hepatic encephalopathy, and multiple organ system failure. And the rationale here is, again, RCT-level data demonstrating a decrease in ICP when you target your serum sodium to 145 to 155 compared to normal sodium levels. Moving on to targeted temperature management, here the recommendations we suggest not routinely using induced moderate hypothermia defined as less than 34 degrees in this patient population at risk for developing intracranial hypertension. Again, a conditional recommendation. The rationale here is that observational studies and multicenter RCT did not demonstrate benefit with respect to ICP decrease or survival. Moving on to switching gears, now we're talking about ACLF in contrast to ALF here. The recommendation one is to suggest using lactulose in critically ill ACLF patients with overt hepatic encephalopathy, again, conditional recommendation. And there is meta-analysis-level data of improvement in HE and mortality in cirrhotic patients. Recommendation two, there is some emerging data regarding the use of polyethylene glycol as an alternative to lactulose in critically ill ACLF patients with overt HE, again, conditional recommendation. Again, this is RCT-level data, single center, that demonstrates an improvement, a faster improvement in HE compared to lactulose. And then the last recommendation in this category is use of rifaximin, and what we recommend is we suggest using rifaximin as adjunctive therapy as an add-on to lactulose or PEG in critically ill ACLF patients with overt hepatic encephalopathy, again, a conditional recommendation based on single center RCT data. Moving on to ID. So antibiotic prophylaxis for upper GI bleeding in the ACLF, and here it's a strong recommendation for a change. We recommend using antibiotic prophylaxis in critically ill ACLF patients with any type of upper GI bleeding, variceal and non-variceal, and I think as a lot of you know, upper GI bleeding is a risk factor for subsequent bacterial gut translocation that can then cause a cytokine surge and cause increased mortality, and there's meta-analysis-level data suggesting the benefit of antibiotic prophylaxis in reducing re-bleeding and in reducing mortality. Moving on to SBP, management in ACLF, recommendation one is using albumin in critically ill ACLF patients with SBP, that's a strong recommendation, and here's meta-analysis-level data that reduces both AKI and mortality. Recommendation two, use of broad-spectrum antibiotics in the initial management of SBP in ACLF, and this is, again, a strong recommendation, again, based on pooled observational studies. And just to make a point that I think a lot of you take care of nosocomial SBP, imagine the cirrhotic who's been in the hospital for a while, here you have to be careful about targeting MDR infections with a broader spectrum of antibiotics. And finally, for recommendation three, we suggest not performing large-volume paracentesis in critically ill patients with SBP, that's, again, conditional, and the rationale here is that LBP can further make a tenuous hemodynamic status worse as you do a large-volume paracentesis. And then finally, systemic antifungal prophylaxis after liver transplant, here the recommendation suggests using systemic antifungal prophylaxis in critically ill liver transplant patients with the risk factors for invasive fungal infections, conditional recommendation. And here the risk factors that have been identified are renal failure requiring dialysis, acute liver failure, re-expiration after transplant, re-transplantation, and a bile leak after liver transplant. And just the common pathogens can be in Canada, followed by aspergillus. And then, as you all know, invasive fungal infection is an important cause of morbidity and mortality after liver transplant, and it's becoming more of a problem as our patients are getting sicker and sicker, awaiting transplantation. And there's meta-analysis-level data demonstrating that systemic antifungal prophylaxis reduce risk of IFI and mortality attributable to invasive fungal infections. Thanks for your attention. Thank you all very much. Dr. O'Grady, I'll have you come up to the podium for fever. And as I stated earlier, we will take all questions at the end of the session. Thank you. Thank you. And good morning. Good morning, everybody. I'm Naomi O'Grady. I'm from the National Institutes of Health Clinical Center, and I will be presenting the SCCM and IDSA guidelines for evaluating new fever in adult patients in the ICU. I have no conflicts to disclose, and I want to give a shout-out to all of the panelists and co-authors that were on this guideline. This guideline appeared in print in November in the Critical Care Medicine Journal. It's available on the website at both the SCCM and the IDSA websites. And there's a lengthy supplement that's also available that goes along with the guideline detailing the methodology and the recommendations. So the objectives for this talk are to, number one, become familiar with the 2023 updated guidelines for evaluating new fever in the ICU. Understand that in contrast to the 2008 guideline, of which this is an update, this guideline uses GRADE methodology, and that the panel produced 12 recommendations and nine best practice statements. Understand that not all febrile episodes require an aggressive fever investigation. For example, there are some things that are quite obvious in clinical practice. A post-operative patient on post-op day one with a new fever doesn't require necessarily an aggressive fever workup. And also know that a good history and physical will determine the type of testing that is needed. These are some of the topics that I'm going to touch on briefly during this talk. All of these were covered in great detail in the guideline. It includes measurement of temperature, the treatment of fever, imaging studies, blood cultures, urine cultures, testing for viruses, and biomarkers of inflammation. So I'll start with a case presentation. A 29-year-old male diagnosed with sickle cell disease presented to the NIH Clinical Center with chest pain and shortness of breath. He has a history of acute chest syndrome for which he's been admitted multiple times. On admission, his blood pressure is 100 over 65, heart rate's 110, respiratory rate 36, temperature 38.3, oxygen saturation 88% on four liters nasal cannula, and he's transferred to the ICU for analgesia, bronchodilators, empiric antibiotics, and transfusion. On arrival to the ICU, his temperature is now 39.0. And here is his rather unremarkable chest X-ray. So how should we approach the workup for this fever? In many ICUs, in many hospitals, a knee-jerk approach would be approached, would be started with a set of orders, an order set that would encompass lots of diagnostic testing. So one of the purposes of this guideline was to guide a little more narrowly the diagnostic testing that goes into fever management. So for those of you who are not familiar with GRADE methodology, what is it? It's the formulation of PICO questions. PICO questions stands for Population Intervention Comparison and Outcome. So we looked for studies that had specific outcome measures when we evaluated the literature. We had a professional librarian develop search strategies for each and every question. We searched the recent literature, i.e., 10 years old or less, and then we used updated meta-analyses or pooled randomized controlled trials, if appropriate. The methodologists assessed the quality of evidence, and the panel voted on the strength of each recommendation. So what is the definition of fever? For the purposes of this guideline, our panel used 38.3 degrees Celsius, but it was important for us to emphasize the emphasis of individualized care, in that young people will have a more robust fever, while elderly patients may have a more muted response. So we encourage people to try to avoid fixed cutoffs and to follow trends in patient's temperature. It's much more meaningful to look at the change than the absolute number. When fever is detected, most people jump to infection as the root cause, but there are other causes which this guideline touches on. So I'll talk a little bit about measuring temperature, because we do get a lot of questions about that. And the one issue that the panel tried to address is, what is the most accurate way of measuring temperature? And I'm sure these pictures are familiar to everybody during COVID days, when we all wanted to take people's temperatures from far, far away, and make sure we didn't come anywhere near them, but yet get an accurate temperature measurement, usually outside in the freezing cold weather. For those of you who saw the humor in that, as I did, I think we can all chuckle in retrospect. So what is the most accurate way to measure temperature? Well, the panel issued a recommendation that said central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, and esophageal balloon thermistors, are preferred when these devices are in place, and accurate temperature measurements are critical to diagnosis and management. For patients without these devices in place, we suggest using oral or rectal temperatures over other temperature methods that are much less reliable, such as axillary, tympanic membrane temperatures, noninvasive, temporal artery thermometers, or chemical dot thermometers. This was a weak recommendation with very low quality evidence, unfortunately. What we will say is that we did take the level of evidence from this particular systematic review and meta-analysis and updated it with a few other studies. We are not recommending the routine use of central thermometers. So what this PICO question highlighted was whether or not precise temperature assessments improve clinical outcomes. If the most accurate evaluation of body temperature won't change clinical practice, the use of an invasive method to assess it could be inappropriate. And the analogy I would like to draw your attention to is how frequently we use noninvasive blood pressure monitoring. We don't always use invasive blood pressure monitoring, and noninvasive blood pressure monitoring is very, very helpful. In the same way, temperature assessment, depending on the patient population, doesn't always have to be absolutely precise, and following trends might be much more important. We next address the question of treatment of fever. Should we treat fever with ibuprofen or acetaminophen? The data shows no benefit, at least not to the patient. There may be some benefit in treating fever for the patient, for the people around the bedside, but should fever be routinely treated with antipyretic medications? There might be some special circumstances if the fever causes hemodynamic instability. For example, putting additional cardiac workload burden, which may trigger an infarction in certain patient populations. Fever that might trigger seizures in patients should also probably be treated. We used this meta-analysis and updated it, but the bottom line from this was that antipyretic therapy effectively reduced temperature in non-neurocritically ill patients, but does not reduce 28-day mortality, hospital mortality, or shock reversal. Of course, as we embark on a fever workup, suspicion for infection should always be at the top of the list, and we did emphasize the importance of empiric treatment with antibiotics, noting that time is of the essence. We want to rule out other causes of fever, but be aggressive about starting and stopping antibiotics while that workup is being undertaken. So what imaging studies should be used in the ICU in terms of working up fever? Again, a good history and physical will guide which imaging studies one would use, but a chest radiograph is a good starting point, as many patients who are in the ICU are at risk for pneumonia, pleural effusions, abscess. These can usually be done at the bedside, and that's an important consideration when we thought about imaging studies for patients' evaluation. The need to transport patients is something that we would like to avoid, and sometimes having the ability to do it at the bedside overrides some of the other considerations. Other imaging studies are based on history and physical. Head ultrasound may be extremely helpful, particularly in postoperative patients, patients who have abdominal signs and symptoms, and sometimes even if expertise exists in the ICU staff, lung ultrasound is quite helpful. Chest CT scans for chest, abdomen, and pelvis are used based on pretest probability of finding something, and PET scans are not routinely recommended but could be helpful in rare circumstances. The next topic we addressed was blood cultures, and the question was, should blood cultures be obtained from central venous catheters? The answer was, in general, yes, even though there is a strong bias against drawing blood cultures from catheters because they are more prone to contamination. But collecting only peripherally minimizes contamination, but it doesn't allow you to sort out where the fever is actually coming from. So using a differential time to positivity, in other words, drawing blood cultures peripherally and from the catheter, if the blood culture from the catheter turns positive more than two hours ahead of the peripheral culture, it gives you a very good, strong indication that perhaps the catheter is the source of the infection. It's notable that yield is dependent on the volume of blood collected. If volume is too small, you may get a false negative result, and the number of lumens sampled improves the yield as well. Please sample all lumens if possible, although your microbiology lab may not appreciate that. Collect blood cultures before antibiotics are initiated. This is important, but do not delay the initiation of antibiotics in lieu of blood cultures. Should urine cultures be sent? This is always somewhat of a conundrum in the ICU. Urine cultures are complicated to collect properly, and they are complicated to interpret. But pyuria and symptoms are important in patients who can communicate. In patients who cannot communicate, pyuria could be important, but your level of suspicion for the urinary tract being the source of fever is more important. So patients who have histories of stones, et cetera, obstruction of the urinary collecting system, those are patients who would be at a higher suspicion for having the urine be the source of fever. In patients with Foley catheters in place, we suggested placing a new catheter before collecting samples. That's a critically important issue in terms of getting a clean catch or a clean sample and having the best information available to assess. We addressed the issue of viral panels in patients in the ICU. Viral pathogen testing should be a part of fever evaluation in patients with suspected pneumonia or respiratory symptoms. There's no question about that. Any patient with respiratory symptoms should have a viral panel sent. Viruses may be single or they may be co-pathogens. Now it's important to detect these because some viruses have therapies available, so it's very important to identify. It's also notable, though, that viruses are transmitted in the healthcare setting. New fevers in hospitalized patients could be viral related. So we didn't really, we did not specifically suggest that only patients with pneumonia or respiratory symptoms get a viral panel sent. Patients in the ICU could have easily picked up a virus from the healthcare environment, the healthcare workers, visitors, guests, et cetera. So it's important to do viral pathogen testing as part of a fever evaluation. The last topic we addressed was biomarkers of inflammation. We developed at least five, maybe six PICO questions on this topic and settled on a recommendation that says in patients with low probability of infection, it's reasonable to check either a procalcitonin or a C-reactive protein. An elevated biomarker should trigger an aggressive search in this patient population, but biomarkers that are normal should trigger a reduction in empiric antibiotics more quickly than if otherwise. Biomarkers alone are not sufficient to rule out infection. In patients who have a high probability of infection, we do not recommend checking biomarkers because it really isn't going to impact the clinical care. So I know that that was fast, but to conclude, I would say there are important advances that have been made, but there are plenty of knowledge gaps that remain, and there is a need for rapid advancement in all areas of testing, also measurement of temperature and the need for reliable, noninvasive core measurement devices, better use for diagnostic imaging, especially at the bedside, and better randomized controlled trials comparing one methodology to another. Appropriate use of rapid molecular testing and the use of biomarkers round up the need for advancement in all areas. So I thank you for your attention. I know that was fast, but I'd be happy to take questions at the end of this session. Thank you very, very much. Dr. Pastores, if you can come up to the podium. Our last guideline will be corticosteroids in critical illness. Hi, everyone. Thanks for joining us today. My name is Dipayan Chaudhary. I'm an intensivist based out of McMaster University in Hamilton, Canada, and I'll be presenting the first part of our 2024 Focused Update Guidelines on Use of Corticosteroids and Sepsis, ARDS, and Chamaenia-Acquired Pneumonia on behalf of our guideline panel. I have no academic or financial conflicts of interest to disclose. So I'll start off with a bit of background. So this all started first in 2008 with a consensus statement released by the American College of Critical Care Medicine. This was a 16-panelist consensus statement based out of intensivists and endocrinologists, and they made 12 recommendations on the diagnosis and management of critical illness-related corticosteroid insufficiency. A modified Delphi methodology was used to achieve consensus. No clear PICOs were established for this statement, and a general literature review rather than a comprehensive systematic review was conducted for each recommendation. Finally, a modified grade system was used to quantify the strength of the recommendations. This was then updated in 2017 with a joint guideline released by the SCCM and ESICM. This was, again, a 16-panelist guideline comprised of members of SCCM as well as ESICM. It updated the diagnosis of corticosteroid insufficiency-related critical illness and discussed the management of eight important clinical conditions. This included not just sepsis, ARDS, and community-acquired pneumonia, but also things like trauma, post-cardiac surgery, as well as cardiac arrest. This updated guideline used a rigorous application of grade methodology with clearly defined PICOs with patient-important outcomes, a comprehensive systematic review for each PICO, as well as a consistent framework used for making recommendations from the evidence. However, since 2017, there have been multiple sort of seminal trials released on the management of corticosteroids and critical illness, particularly in the areas of septic shock, ARDS, particularly COVID ARDS, as well as community-acquired pneumonia. So that led us to conduct this 2024 focused update, focusing specifically on sepsis, ARDS, and community- acquired pneumonia. These conditions were picked because they were the most common diagnosis in which corticosteroids are considered and in which there is sufficient new data. We did not reassess the definition and diagnosis of CIRCI, and we used an updated grade methodology with a more rigorous evidence of decision-making framework to conduct these guidelines. We established a 22-member panel consisting of two endocrinologists and 20 critical care practitioners, of which 20 were voting members. Two did not vote because of conflict of interest. We had a guideline leadership group consisting of two chairs and two co-vice chairs, as well as a four-member methodology team. We came up with five PICO questions. The first one was, should corticosteroids be administered to hospitalized patients with sepsis? The second was, if patients with sepsis are administered corticosteroids, should high-dose short-duration be used over low-dose long-duration? The third was, should corticosteroids compared to no corticosteroids be used in patients with ARDS? Should methylprednisone be used over corticosteroids in patients with ARDS? And should corticosteroids be administered to hospitalized patients with community-acquired pneumonia? Once we had come up with these PICO questions, we polled the guideline panel and came up with a list of outcomes that we thought would be important to assess to address these PICO questions. And then we asked them to rank each outcome from a scale of 1 to 9, with 9 being the most important and 1 being the least important. We averaged out all the ratings from all the guideline panel members, and then we ranked the outcomes in terms of importance as a result. Then we conducted systematic reviews on our PICO questions. We used previous reviews that were done by members of the guideline panels as a springboard to move ahead. We conducted a standard systematic review and meta-analysis protocol using a professional librarian to create an updated search strategy. We dual-extracted our data and pooled and meta-analyzed everything, and then we analyzed our other studies for risk of bias. We use this to then generate evidence profiles, which presents a summary of our findings, which were essentially our effect sizes, both relative and absolute, as well as the certainty or the quality of the evidence we generated. Here you can see some examples of what an evidence profile would look like for each individual outcome that we tested for each individual PICO. Once we had generated our evidence profiles, we met together as a guideline panel and considered not just the quality of the evidence and the evidence profile, but also the costs of the interventions we were looking at, patient values and preferences, as well as healthcare provider values and preferences, the risk and benefits of the intervention, its feasibility, as well as equity, to come together and make a recommendation. I'm Steve Pastoris from Sloan Kettering in New York City. It's a delight and a privilege on behalf of the 22-member panel of our task force to present to you the top-line results for the corticosteroid guideline update. These are my disclosures. There's nothing specific to the content of my presentation this morning. These are the top-line results. For patients with septic shock, we suggest administering corticosteroids in adult patients with septic shock. We gave this a conditional recommendation based on low-certainty evidence. We had a strong recommendation and reinforced that corticosteroid at high dose at short duration should not be used for patients with septic shock. For ARDS, we suggested administering corticosteroids to adult hospitalized patients with ARDS. This was given a conditional recommendation with moderate certainty evidence. And for community-acquired bacterial pneumonia, we gave a strong recommendation for administering corticosteroids to adult hospitalized patients with severe bacterial community-acquired pneumonia. So let's go over quickly because there was a slight change in how the 2017 recommendation read to what we had proposed. Most of the trials and systematic reviews that we looked at, and there were 46 RCTs related to sepsis and septic shock. Most of them were actually septic shock studies with only about six or seven sepsis. So our recommendation was specific to giving corticosteroids to adult patients with septic shock. Note that we could not give a specific recommendation to give corticosteroids in patients with sepsis without shock because most of the literature that we found were related to giving steroids in those patients already that were in full-blown septic shock. The other change was that in the 2017 guideline, we had suggested the use of corticosteroids specific to patients that were not responding to fluid and vasopressor therapy, moderate to high-dose vasopressor therapy. At that time, we gave that a conditional recommendation with low quality of evidence. So we shifted to basically no longer requiring the vasopressor dose, whether it's high dose of one or two. And we gave a strong recommendation against the use of short-duration, high-dose corticosteroids. That kind of reinforced what we had already suggested in our 2017 guideline. The rationale is that, again, most of the patients that we analyzed were patients with septic shock, that it showed some small, moderate effects in terms of short-term mortality. But although a small reduction in mortality with low to moderate certainty evidence was found, we had a large reversal of septic shock and organ dysfunction with high certainty. And given the high prevalence of septic shock worldwide, the small reduction in mortality, and the shock reversal in organ dysfunction reduction, we felt that that had important implications regarding resource utilization. We all know the undesirable effects of corticosteroids. Certainly hyperglycemia is very common, hypernatremia, as well as neuromuscular weakness. But in analyzing the studies, we found that there was a bit of heterogeneity in how these side effects or adverse effects were defined and how they were managed, and that there were no really long-term data on many of these side effects. We felt, however, that given the simplicity of the regimen, the feasibility of giving them even in low-resource countries, we felt that it was appropriate to recommend and suggest the use of corticosteroids in patients with septic shock. Now although we did not give a specific recommendation in patients with sepsis without shock, we did suggest that in patients presenting with sepsis and severe community-acquired pneumonia, or with sepsis and ARDS, we suggest administering corticosteroids on those patients. Unfortunately, in looking at the literature, we found very limited available studies to make a specific recommendation in pediatric patients with septic shock. The dose that we found that was commonly used, again, were based largely on the two large randomized trials published in 2018, the French trial and the Australian New Zealand trial, which used hydrocortisone, 50q6, or 200 milligrams IV continuous infusion, with or without the addition of flutocortisone for up to seven days or until ICU discharge. Again, this is the most commonly used regimen, but again, in certain settings, the duration varies. But this is what we came up with as a recommended dosage for those that use hydrocortisone. For ARDS, our suggestion was to use corticosteroids to, again, adult patients with acute respiratory distress syndrome. Slight change again, because in the 2017, we were very specific in suggesting the use of steroids for early to moderate ARDS, as suggested by a PF ratio less than 200, and within 14 days of the onset of ARDS. So we've gone away from that and just suggesting up front that if you have a patient with ARDS that fits the Berlin criteria for ARDS, the corticosteroids should be initiated as early as possible, unless there's a reason not to. We thought that in the ARDS systematic reviews and meta-analysis, many of them published by authors of the guideline, we found moderate desirable effects, largely driven by moderate certainty evidence that it reduces hospital mortality, and more importantly, based on mechanical ventilation. The effect was more pronounced when the steroids were used for a longer duration, i.e., more than seven days. But again, we could not find the appropriate type of molecule, the timing of when the steroid is started, the duration. So these were largely unknown because of the heterogeneity of the various studies in the dose of steroids. So we felt that that was to be left to the clinician discretion and other considerations. So that is in contrast to our 2017 guideline, where we specifically mentioned the use of methylprednisolone, one milligram per kilogram per day, within 14 days of onset of ARDS. Again, similar to sepsis and septic shock, the adverse events such as hyperglycemia, neuromuscular weakness, GI bleeding, and cost effectiveness remains relatively unknown. I think what seems to be consistent is concern for bacterial superimposed infections, GI bleeding, appear to be very, very low. Hyperglycemia, yes, is quite common, typically requiring some intervention, but not of serious import in most settings. And neuromuscular weakness, again, most of the studies were short-term. We don't know what long-term, and there's a knowledge gap in that direction. We thought, again, given the simplicity and use and availability of corticosteroids, we felt it was definitely something that should be considered. Again, the benefits outweighing the risk. Again, no RCTs in the pediatric population, so we could not make a recommendation. Using the methylprednisolone recommendation, we felt that clinicians have multiple dosing strategies and that specific choices of steroid molecule, timing, and duration should be left at the discretion and other considerations pending further data. These are some of the suggested type, dosing, and duration regimens most commonly used are the study with dexamethasone from the VILAR Spanish trial and the ARDS within 72-hour trial from ESCAPE that Madhuri and colleagues did and was published a couple of years ago in Intensive Care Medicine. So all of these are available in the online supplement as well as on the full guideline that's available online. For community-acquired pneumonia, again, we gave a strong recommendation for giving adult hospitalized patients with severe bacterial community-acquired pneumonia give steroids. This might change in terms of where we were in 2017 in that we switched from a conditional recommendation to a strong recommendation for patients. We could not give a recommendation for pediatric patients, again, for lack of RCTs in that population. So we could also not make a recommendation for patients with less severe community-acquired bacterial pneumonia because that did not seem to suggest a strong direction of benefit and it was unclear based on our analysis. So these are some of the definitions that were used to define severe CAP. We all know this. Patients can be on noninvasive ventilation or high flow with at least 30 or 40 liters of flow rate or be intubated on mechanical ventilation and have, let's say, septic shock associated with the need of vasopressors. These are some of the criteria that were used in the ATS IDSA guideline published in 2007 and in the CAPECOD study published a couple of years ago. I put up the forest plots here because I want to let you see that in red boxes when we look at short-term hospital mortality and need for mechanical ventilation for patients with severe community bacterial pneumonia, there was a strong signal for the benefit of corticosteroids in those patients. Ten of the trials, of the 18 trials, had severe CAP definitions met and eight had less severe. The signal on less severe community acquired bacterial pneumonia was not strong, was very, very slight, and so was the need for mechanical ventilation, but it was quite strong for reduction in mortality and need for days on mechanical ventilation. So we thought the desirable effects were large in these patients and that the mortality benefit was only seen in severe bacterial pneumonia but not in less severe community acquired pneumonia. We thought in this particular subset of patients there was a moderate certainty that hyperglycemia is common. I guess these studies had more specific definitions and more homogeneity of it in their definitions of hyperglycemia and treatment intervention. So we thought with moderate certainty hyperglycemia indeed is a risk and side effect of corticosteroid use, but with low certainty we could not find an increase in secondary infection as well as uncertainty in the presence of or occurrence of GI bleeding. We thought, again, the use of steroids is safe, relatively safe. It's feasible and can be associated with cost savings, particularly in low resource areas where they don't have as much pharmacological agents to use for these patients. As with sepsis and ARDS, the panel could not make a recommendation for the use of corticosteroids in community acquired pneumonia based on the lack of available literature in these patients. There are multiple regimens that are suggested. I think most commonly used agent now is hydrocortisone, although the trials, again, varied in terms of the type of hydrocortisone or methylprednisolone, those that we use, the timing of when it was initiated and the duration of treatment. But they're out there for you to see because this is probably what you use. And most of it is based on the most recent trials that came out two, three years ago. Again, just one more look at the summary of recommendations. And lastly, there are so many knowledge gaps. We don't have enough literature and RCTs in pediatric patients who are hospitalized with sepsis, septic shock, community acquired pneumonia, and ARDS. We don't have literature as much in patients with surgical sepsis without shock. There seems to be some conflicting results in the use of corticosteroids in patients with sepsis and neurological conditions. And the optimal dose and timing, again, needs to be evaluated a little bit more carefully, as well as the short-term and long-term side effects, in particular neuromuscular weakness. And that's a subject of current and ongoing studies. I want to acknowledge the contribution of our SCCM staff, as well as our liaisons from the American College of Critical Care Medicine, one of our moderators here, M.J. Reed was part of that, and of course, our librarian support services from McMaster and St. Joseph's Healthcare System. Thank you very much for your attention. Thank you.

peritransplant GI considerations

neurologic complications

infectious diseases

sepsis management

acute respiratory distress syndrome

community-acquired pneumonia

corticosteroids guidelines

portal hypertensive bleeding

fever evaluation ICU