Good morning, everyone. Thank you for coming. I know finding us has been a little bit of a challenge this morning, coming into the bend of the wall to get to room 310. It is 1030, and we want to be respectful of your time. So this is the from intubation to extubation, a review of the most recent literature. Dr. Casey will be presenting on the strategies during the intubation period. Remember that all rights are reserved here, all visual content that we have that we are presenting is exclusively the property of CHESS. No personal recordings of the content in the meeting are allowed. Please make sure that if you do need anything, do you have a question, we will have questions at the end of our session this morning. I would like to go ahead and introduce our first presenter. Give me one second. So this morning, we did change the session around just a little bit so that we were talking about intubation, then mechanical ventilation, spontaneous breathing trials, and then how to keep people extubated. So this morning we have Dr. Jonathan Casey. He's a physician scientist in the Division of Allergy, Pulmonary, and Critical Care Medicine in the Department of Medicine at Vanderbilt University Medical Center. Dr. Casey directs the Coordinating Center for Pragmatic Critical Care Research Group, which focuses on the comparative effectiveness of standard of care interventions among critically ill adults. His work has been published in the journals such as New England Journal of Medicine and JAMA. Please welcome, as we introduce Dr. Casey, to present on the strategies during intubation period. Thanks for the kind introduction. Thanks for having me today. I want to thank the organizers for planning this session and thank all of you for being here. We're hard to find, so I know that you really must have wanted to see this lecture today. So as mentioned, we'll be talking about respiratory support during airway management of critically ill adults. My name, again, is John Casey. And as mentioned, I'm an Assistant Professor of Pulmonary and Critical Care Medicine at Vanderbilt University Medical Center and direct the Coordinating Center for the Pragmatic Critical Care Research Group. My only disclosure relevant to this talk is that I have a travel grant from Fisher and Paykal to attend a recent conference. So today we're going to talk about why respiratory support is important during emergency tracheal intubation of critically ill adults. We'll review the devices and approaches that can be used and their relative risk and benefits. We'll discuss the existing evidence from randomized trials and give you a preview of one trial that's finishing soon. So I think, as you all know, emergency tracheal intubation is a common and high-risk procedure. When patients undergo tracheal intubation in the operating room, the risk of complications is low, occurring in approximately 2% of patients. When we perform that same procedure in the ED or ICU, complications occur in up to 40% of patients. And that high complication rate is despite this being an extremely common procedure. So in the US alone, 1.5 million patients or critically ill patients are intubated each year. And in study after study, cardiac arrest occurs in 2% to 4% of those patients. So when you walk into an ICU room, and you're preparing to do this two-minute procedure, you know that your patient has something like a 1 in 50 chance of dying in the next two minutes. So there's very few things we do that are higher risk in medicine than intubate a critically ill patient in the ICU. And of the drivers of cardiac arrest, hypoxemia is thought to be the number one risk factor. There are various phases of tracheal intubation. There's the initial phase, where we're setting up and preparing for intubation. There's the phase following induction, between induction of anesthesia and initiation of laryngoscopy, where the patient's breathing is slowing, and the patient then becomes apneic. And then the third phase, during which laryngoscopy is occurring, and the patient's completely apneic. As expected, the risk of hypoxemia increases during this period, and really is highest towards the end of the third phase, before the initiation of mechanical ventilation. There are various devices that can be used to try to prevent hypoxemia during emergency tracheal intubation. These devices deliver either oxygen alone, or oxygen and ventilation. Devices that deliver oxygen include high flow nasal cannula, and standard nasal cannula, and face mask oxygen. Devices that deliver oxygenation and ventilation include non-invasive ventilation and bag mask ventilation. And based on the nature of the devices, that determines which phases they can be applied during. So all devices can be used during the first two phases, but only high flow nasal cannula and standard nasal cannula can be in place during the third phase, when a laryngoscope's in the mouth, and face mask devices have to be removed. We've labeled these three phases distinctly. The first phase, the three to five minutes before we start intubation, we call pre-oxygenation. This second phase doesn't have a great term. Today we'll discuss it as oxygenation and ventilation between induction and laryngoscopy. And the third phase, when the patient's apneic and the laryngoscope is in the mouth, we term apneic oxygenation. We'll start with discussing pre-oxygenation. Pre-oxygenation's the most effective intervention to reduce the risk of hypoxemia. At the onset of apnea, the patient reaches the functional residual capacity, or FRC, through a passive exhalation. And the oxygen content in the lungs, that FRC, is the reservoir to prevent hypoxemia during intubation. Pre-oxygenation, sometimes called denitrogenation, is the administration of 100% oxygen with the goal of increasing alveolar oxygen reserve for devices that include positive pressure. It has the dual benefit of also increasing lung volumes at FRC. There have been a number of trials that have compared the available devices for pre-oxygenation. These trials have largely been small to moderate in size. There have been two trials comparing non-invasive ventilation and face max oxygen for critically ill adults, both conducted by the same group, BILARD. In their initial single center study of 53 patients, they showed a significant reduction in hypoxemia. They followed that up with a 201 patient multi-center trial that failed to show a significant difference, although still showed a 10% difference that could be clinically significant if validated. High-flow nasal cannula has been a device that's created a lot of excitement around emergency tracheal intubation and the OR and other settings. There have been three modestly sized trials comparing high-flow nasal cannula to face mask oxygen. All three have failed to meet their primary outcome of reducing hypoxemia. And finally, there's been one trial comparing non-invasive ventilation and high-flow nasal cannula, the FLORALI-2 trial by FRAT, this 322 patient trial, randomized patients to non-invasive ventilation and high-flow nasal cannula and found no difference in the primary outcome of hypoxemia, but in subgroup analyses found that non-invasive ventilation might be better than high-flow nasal cannula among patients with severe acute hypoxemic respiratory failure. So I think we can make some tentative conclusions from these trials put together. Non-invasive ventilation is probably better than high-flow nasal cannula, which is probably better than a non-rebreather, which is clearly better than a nasal cannula. So the pretty simple summary is more oxygen is better. And oxygen ventilation might be better than oxygenation alone, but the total number of patients enrolled in these trials is pretty modest considering this is a procedure that occurs millions of times every year. And these trials have been small, too small to evaluate safety risk like the risk of aspiration with non-invasive ventilation. I'll highlight there's an ongoing trial that I hope will help improve evidence in this space. This is the PREOXY trial, the pragmatic trial examining oxygenation prior to intubation. It's an ongoing trial of preoxygenation with non-invasive ventilation versus face mask oxygen. It enrolls patients undergoing emergency tracheal intubation in 24 EDs and ICUs across the United States. And it's conducted by our group, the Pragmatic Critical Care Research Group, which is a clinical trial network composed of multidisciplinary investigators from emergency medicine, anesthesiology, and critical care. And as mentioned, we specialize in pragmatic trials comparing the effectiveness of emergency interventions. The PREOXY trial is a 1,300 patient trial. The primary outcome is hypoxemia and oxygen saturation less than 85%. The lowest secondary outcome is the lowest oxygen saturation between induction and laryngoscopy. And the safety outcome is all focused on aspiration, operator-reported aspiration, new chest X-ray infiltrate, et cetera. I was hoping to be able to announce that we finished enrollment this week, but we're close but not quite there. So we're currently at 1,285 out of 1,300 patients. So we expect to finish enrollment in the next one to two weeks. And hopefully we'll have results early next year. So that was our summary of preoxygenation. We'll discuss now this period between induction of anesthesia and laryngoscopy and discuss the approaches to oxygen and ventilation during that period. There's only been one trial conducted during this period. And RSI involves this inherent delay between induction of anesthesia and laryngoscopy. During this period, the patient's slowing their breathing and becoming apneic. And for 50 years, there's been this debate about what to do, either observe and nothing or provide bag-mask ventilation. And the controversy has existed because of hypothesized competing effects. Bag-mask ventilation might prevent hypoxemia, but bag-mask ventilation might also cause aspiration. Our group conducted the PREVENT trial, the Preventing Hypoxemia with Manual Ventilation during endotracheal intubation trial to explore this question. The trial was conducted at seven intensive care units across the United States. We enrolled all adults undergoing tracheal intubation with sedation. Exclusion criteria included pregnant women, prisoners, intubations that were too emergent to perform randomization, and any intubation where the provider felt that ventilation after induction was required or contraindicated. During the procedure, data was collected by an independent observer. Patients were randomized one-to-one to bag-mask ventilation or no ventilation. The primary outcome was the lowest oxygen saturation between induction and two minutes after intubation. And the secondary outcome was the incidence of severe hypoxemia or an oxygen saturation less than 80%. Safety outcomes focused around aspiration, including operator-reported aspiration, highest FiO2, highest PEEP, and lowest oxygen saturation from 6 to 24 hours, and new infiltrate on chest X-ray. A total of 401 patients were randomized. Their baseline demographics are shown here. Approximately half of patients had sepsis or septic shock. The most common indication for intubation was respiratory failure. And approximately 60% of patients had at least one risk factor for aspiration. 99.5% of patients randomized to bag-mask ventilation received bag-mask ventilation, compared to 2.5% assigned to no ventilation. So after 50 years of controversy regarding whether bag-mask ventilation should be provided and whether or not it was effective in preventing hypoxemia, the trial results are shown here. On the left are patients in the bag-mask ventilation group. On the right are those in the no ventilation group. Every dot represents the lowest oxygen saturation experienced by one patient in the trial. As you can see, patients in the bag-mask ventilation group had a higher lowest oxygen saturation at a median of 96%, compared to 93% in the no ventilation group. It's possible that bag-mask ventilation could increase the median oxygen saturation for every patient by a few percent, or it could prevent extreme cases, or it could do both. So looking at the same data in a different way would be to split it dichotomously by severe hypoxemia criterion. As you can see here, bag-mask ventilation was most effective at preventing the most severe cases of hypoxemia. It reduced mild hypoxemia by about a third, severe hypoxemia, the sole pre-specified second or outcome by half, from 23% to 11%, and very severe hypoxemia by approximately three-quarters. As mentioned, the main controversy around the PREVENT trial had been, is bag-mask ventilation effective at preventing hypoxemia, and is it safe? Does it cause aspiration? The trial was too small to be definitively powered to evaluate aspiration, but it's reassuring that operator-reported aspiration occurred at 2.5% of patients in the bag-mask ventilation group, compared to 4% in the no ventilation group. And all other outcomes focused on aspiration, such as new chest x-ray infiltrate, and physiologic parameters of oxygenation were similar between the two groups. Finally, we'll focus on the third phase, the so-called apneic oxygenation phase. Apneic oxygenation can be provided with either a standard nasal cannula or a high-flow nasal cannula. There are two trials that have looked at apneic oxygenation during laryngoscopy. The FELLO trial, conducted by our group in the ICU, and the NDAO trial, conducted by an emergency medicine group in New York, both failed to show any benefit from providing 15 liters nasal cannula during the apneic oxygenation period. There's been hope that high-flow nasal cannula might be more effective at preventing hypoxemia during this apneic oxygenation period. And these are the same three trials we mentioned before. The high-flow nasal cannula can be used for both pre-oxygenation and apneic oxygenation. And as mentioned, all three trials have failed to show definitive benefit from high-flow nasal cannula, although you might see a trend here that there's a potential benefit that might be small or modest in size. For many years, there's been debate about how to provide oxygenation and ventilation during rapid sequence intubation. And until very recently, there was no literature to really help us make our decisions. When we started doing this work, there had only been one prior trial of tracheal intubation. Thankfully, I think this evidence base is accruing and we can make some summary statements. I think it's fair to say that pending the results of the pre-oxy trial, it's reasonable to consider non-invasive ventilation for pre-oxygenation, especially among patients who are high risk. I think the evidence is pretty clear that we should be providing bag mask ventilation or non-invasive ventilation between induction and laryngoscopy. For those at the highest risk of aspiration, it may be reasonable to provide an alternative strategy like high-flow nasal cannula or face mask. But I'll highlight that at least in the ICU, that represents a small minority of our patients, less than 5%. I hope it's an obvious statement that a nasal cannula alone is never sufficient for pre-oxygenation. And finally, although research is ongoing, it appears that administering apnea and oxygenation during laryngoscopy may only be treating ourselves. So I again thank the organizers for inviting me. I look forward to the questions. All right. Our next presenter is Professor Paul Young. He is a critical care specialist and clinical researcher from Wellington, New Zealand. Over the past decade, he's authored many pivotal clinical trials, including more than a dozen published in the New England Journal of Medicine. In relation to oxygen targets, the topic of his talk today, he was the chief investigator for the ICU ROCKS trial. He's also the chief investigator for the MEGA-ROCKS trial, which is a 40,000-participant randomized control trial, comparing conservative and liberal oxygen regimens in patients who require unplanned life support in the ICU. More than 1,000 patients per month are being currently recruited into this trial. Please join me in welcoming Professor Young, who will present an update on ICU oxygen therapy targets. Thanks very much. It's a pleasure to be here. I'm going to talk to you, as just mentioned, on ICU oxygen targets. And while I don't have any financial conflicts of interest to declare, I do have a passion for this topic and have been involved in researching it for a number of years. So I guess those things definitely color what I have to say. So this green slime is cyanobacteria. It's billions and billions of them. And the only reason that we exist is because cyanobacteria evolved and they started to photosynthesize and they made some oxygen. And so interestingly, I reckon, when they first made oxygen and when multicellular life appeared on planet Earth, it was just a small, small, small amount. Hardly any. And so in a way, we're like just these giant suits walking around with skin on top, with, you know, like goo in the center, and an oxygen cascade that's designed to replicate the way the Earth was 150 billion years ago. And the way it was, was there was very, very little oxygen. So we're walking around being protected from this intrinsically, highly reactive chemical. It oxidizes lipids, it damages DNA, and it basically leads to the accumulated wear and tear that gets us all in the end. So we all live because of oxygen, and in the end, we all die because of it too. So the idea that the dose of oxygen that we give to people who are critically ill and on life support, the idea that that might affect their outcomes, it's highly plausible. And it's highly plausible just from the perspective of the chemistry. So there's been lots of research now looking at oxygen in patients requiring intensive care, and the first study that sort of was of moderate impact was the oxygen ICU trial, which looked at people expected to stay for at least 72 hours in intensive care, and they were enrolled in a single intensive care in Italy. And the first thing that they reported was that the ICU mortality was almost halved with conservative oxygen therapy, which is absurd, right? If this was true, then the number needed to treat to prevent one death would be not very many, it would be 10. And 50% of all the deaths that occurred in intensive care would be caused by oxygen poisoning. So that's not true. So this study had a number of shortcomings. Perhaps the most significant was it was stopped early after an unplanned interim analysis without the use of conventional stopping rules. But it's provocative anyway. And it kind of meant that when we did the systematic review and meta-analysis looking at acutely ill adults, that there was this signal that mortality was lower in patients who received conservative oxygen therapy. So one caveat here was that a lot of the patients in this trial were, in this analysis, were from that oxygen ICU trial. And also, a lot of the other patients were stroke patients and cardiac arrest or myocardial infarction patients. So a lot of uncertainty. But by the time it came to the ICU ROCS trial being imminently published, people believed the idea that conservative oxygen therapy would increase the number of mechanically ventilated free days, or ventilator free days. So I mean, I don't know. That's what people on Twitter believed anyway. So the ICU ROCS trial, just to remind you, this was a trial in adults who were mechanically ventilated and expected to be ventilated beyond tomorrow. And conservative oxygen therapy was designed to minimize exposure to a high SpO2 and increase exposure to lower inspired oxygen concentrations. So basically, what we did was we set an upper limit alarm on the monitor. And we said, whenever the saturation exceeds 96%, you need to turn the oxygen down as low as you possibly can and try to get the patients to breathing room air if you can. We succeeded in enrolling pretty sick patients. So 92% were emergency admissions. Patchy's score was 23.4. And 40% of the patients in our trial had acute brain pathologies. The primary outcome, as I mentioned, was ventilator free days. And the 95% confidence interval here encompassed the possibility of a 2.1 day reduction and a 1.6 day increase in number of ventilator free days to day 28. If you look at the mortality out to day 180, in this diagram that I'm drawing here, red is dead. And it looks like for every 100, you get an extra one dead person in the conservative oxygen therapy group for a relative risk of 1.03, and 95% confident of intervals. You can see they're spanning from a 13% relative risk reduction to a 23% relative risk increase. In the same paper issue of the New England Journal of Medicine, the LOCO2 trial was published. This looked at patients who had ARDS. And it was stopped early. Again, this was stopped early actually at an unplanned analysis because of what was kind of assumed to be an excess of mesenteric ischemic events in the conservative oxygen group and a numerically higher mortality in the conservative oxygen group. Soon followed, though, by the HOP ICU trial, which looked at patients with hypoxemic respiratory failure and compared lower and higher targets. And this group of patients was sort of interesting, I thought. So it was a Scandinavian trial. The patients were pretty old. One in five of them actually had COPD. More than 50% had pneumonia. There were 10% who'd had a cardiac arrest before they were enrolled. But overall, there were relatively few patients in this trial who had brain pathologies like stroke and TBI. This is the sort of separation in oxygen exposure that they had in this trial, which was slightly less than they were aiming for, primarily because the lower group wasn't as low as they'd intended. And this is a common feature in these oxygen trials because there's a ceiling. I mean, there's a floor effect, right? So you can't make the PaO2 low enough without using a hypoxic gas mixture in a number of patients. So it's often quite hard to achieve the low target. Here again is a similar diagram to the one that I showed for the ICROCS trial. Again, there is numerically one extra dead patient out of every 100 randomized in the low oxygen group. Next, the pilot trial. So this is oxygen saturation targets for critically ill adults receiving mechanical ventilation. A three-arm multiple crossover trial from a single center in the States. And this diagram here sort of summarizes the way the trial works. So they cycle through in three monthly blocks. I think it is, or monthly. Three monthly blocks. And there's one little point there where they pause recruitment because of the coronavirus pandemic. The thing that was sort of interesting about this trial is there's a few things. The first thing is that by doing a cluster trial, they could enroll people at the time that they received mechanical ventilation. And this is really important because we know from the observational data that most exposure to abnormally high levels of oxygen in clinical practice occurs soon after intubation. So this is a really interesting feature of the trial. And I guess another major strength of the trial is that the cluster design eliminates selection bias. So there's a lot of generalizability, at least for centers that are similar to Vanderbilt, I guess. And so unfortunately for me, when I looked at the baseline data, they're extraordinary because they're nothing like my environment. So it's non-surgical patients. Again, 20% had COPD. 14% of the patients were on home oxygen at baseline. It would be true for me to say that in my entire career, I've never seen a patient in my intensive care unit who's ventilated, who's usually on home oxygen. 13% of patients had post-cardiac arrest. A third had sepsis. And 3%, their indication for ventilation was that they were usually ventilated in their place of residence, which is, again, extraordinary because in New Zealand, there is zero patients in New Zealand who are on chronic mechanical ventilation. That's not a thing that exists in my country. So there are three groups, low, intermediate, and high. And the targets, respectively, were 90, 94, and 98. And that's what they actually achieved. Again, you can see the lower group didn't go quite as low as they were intending, which is a common feature of these trials. Ventilator-free days was the primary outcome variable. And there's what it turned out for those three groups. So they all look very similar. The most recent trial is the ICONIC trial. This is a European trial, or a trial from the Netherlands, looking at conservative and liberal oxygen therapy. The feature of this trial was the separation between oxygen exposure of the two groups is a little bit larger than seen in most of the trials. But again, consistent with all of the trials that we've seen, there actually was, by point estimate, a higher number of deaths in the low oxygen group. And so I know that there are a lot of people now who will be thinking enough. Surely, we have enough randomized controlled trials of oxygen for patients on life support. No. This is not right. So the reason it's not right is there's a number of things. So one is, as I mentioned before, right at the very beginning, it is highly plausible the dose of oxygen matters. In my mind, it is highly plausible that the dose of oxygen that is correct depends on what is wrong with the patient. Now, there's an interesting editorial in the Blue Journal that accompanies the ICONIC trial talking about some work that we've been doing using machine learning to look at individual treatment effects. And that's work that's coming soon. It's really provocative, interesting data. But I thought one thing I would talk about is that in relation to the sepsis subgroup, we know that neutrophils use oxygen to kill bacteria. That's true. And so it's plausible that restricting oxygen in patients who have sepsis is a bad idea. And so I think it's quite believable that for patients who have sepsis, a liberal oxygen regimen is better. On the other hand, in the post-cardiac arrest population, in the ICU ROCKS trial, we had this really quite striking effect in the subgroups of patients who'd had a cardiac arrest and were at risk of hypoxic ischemic encephalopathy, where the number of deaths and the number of unfavorable outcomes was higher than the usual or liberal oxygen group. And so while there has been a small trial looking at this directly, published more recently, a really notable feature of this trial was the outcomes for all of the patients in this trial were extraordinary. So the number of patients who ended up with a bad outcome here was extremely low. And so the generalizability of this ROCKS trial is quite low. And so I think it's still quite possible that conservative oxygen therapy is best for patients who've had a cardiac arrest. The next reason that we need more trials is that oxygen is the single, and patients who are in the intensive care who are really unwell, it's like the single most common treatment. And so from a public health perspective, a really small treatment effect would matter. And none of the trials, either together or even in aggregate, have come close to detecting an effect that would be important. So even a 1.5 percentage point reduction in mortality or effect on mortality would equate to 1,500 lives lost or saved for every 100,000 patients treated. And so the MEGA-ROCKS trial is designed to detect an effect of that size. So it's a 40,000 patient trial. We have currently enrolled over 17,500 patients in that trial. We're enrolling the number of patients who are enrolled in the ICONIC trial every two and a half weeks at the moment. It's not just one trial. It's a series of parallel randomized controlled trials investigating pre-specified hypotheses for benefit or harm for each group. Nested within the MEGA-ROCKS HIE trial, which is the cardiac arrest trial, we're also doing a trial that looks at favorable neurological outcome at six months, because it's not just whether you're dead or alive if you've had a cardiac arrest that matters. That's all I wanted to say. Thanks very much for your time. And we do need another trial. All right, our next presenter is Dr. Kapoor. She is an Assistant Professor of Medicine, Associate Program Director of Critical Care Medicine Fellowship, the Associate Director at the Office of Interprofessional Learning and Medical Director of the Medical Intensive Liver Unit. Her primary areas of clinical focus is that she's focused on the Center on Diagnostic Assessment Therapeutic Invention and Innovative Research with a special emphasis on critical ill patients with liver disease. As the Director of the Medical Intensive Liver Unit, she holds the responsibility of overseeing the daily operations, and a pivotal aspect of her position is that she fosters collaboration with a diverse multidisciplinary team, ensuring comprehensive and integrated patient care takes place. Please join me in welcoming Dr. Kapoor as she presents the Spontaneous Breathing Trials, Does It Matter, How Is It Done? So it looks like we have intubated the patient. Now it's my turn to extubate. We did a great job so far. For the safety of our presenters and attendees, like this time, I urge ACCP to commit to ensure that future meetings are held in locations where elected leaders understand the importance of freedom and sanctity of patient-physician relationships. So our goal for the next 15 minutes is assess readiness for trial of extubation in patients, appraise the safety of SBT and SAT, and review various methods of spontaneous breathing trials. So raise your hand if you do not agree with me that we should extubate as soon as possible, except for patients who will ask for pain medications. I'm talking about like where we really don't want it. So prolonged mechanical ventilation for critically ill patients is associated with, we all know this, adverse clinical outcomes, including physiological and psychological stress to the patient, higher morbidity in terms of VAP, ventilator-associated lung injury, longer hospital length of stay, increased resource utilization and cost, all the more reasons that we should be acting fast to extubate. This is the data supporting that we don't do it enough, right? Rate of reintubation is really, really low across the world. Rate of reintubation after planned extubation is around only 10%. And it exceeds 20% when we are thinking these patients have high risk of extubation failure. So stating that, the guidelines from American Thoracic Society, SCCM, as well as CHEST, in 2017 recommended to systematically perform a spontaneous breathing trials before extubation in all the patients who are intubated for more than 24 hours in order to mimic post-extubation physiological conditions. So you mimic that condition by doing spontaneous breathing trial to assess the readiness for extubation. This is a bundled, protocolized approach. You just don't go and start doing spontaneous breathing trials. Approaches assess for readiness. There are multiple parameters where we are going to talk how to assess patients if they are ready. Determine what type of method you are going to use for spontaneous breathing trial. Then we'll talk about post-intubation care and prevention of reintubation. So I'll take the first two parts. The next talk would be on post-extubation care. So I just used the word protocolized and bundled care. So what is the evidence behind protocolized bundled care? So how do we do it? So this is a study which did show that protocolized versus non-protocolized meaning for reduction of mechanical ventilation in critically ill patients. The study was done, these were the intents of the study, to compare total duration of mechanical ventilation in critically ill patients who were either gone through SBT by a protocolized approach versus non-protocolized approach. Also compare their outcomes in terms of meaning, duration, harm, unrest, and resource utilization. In addition, the study was also looking at subgroup analysis to see which type of patients were successful under protocolized care, like multiple different type of ICUs, type of protocols, and approach to delivering the protocol, who delivered that protocol, physicians, RTs, nurses. Seventeen trials were under the study involving around four continents. The weaning protocol was professional-led in 13 studies and computer-led in four studies. So the results, as I'm saying we should be doing protocolized, so of course the results are positive of this trial, of this review. So mean duration of mechanical ventilation in protocolized weaning protocol was 26 percent, is reduced by 26 percent as compared to patients where we did usual care. Reduction was reduced by 70 percent, ICU stay-up length reduced by 11 percent. And reductions in the subgroup analysis were more in medical, surgical, and mixed ICU, no offense, not in neurological ICUs based on this protocolized study. So saying that we need to protocolize, there was recommendation again by guidelines from CHEST in 2001 that patients who are receiving mechanical ventilation for respiratory failure should undergo formal assessment, again, protocolized assessment for discontinuation potential, if they meet following criteria. If they have reversal of underlying disease by some means, you can assess that COPD is getting better, sepsis is getting better, adequate oxygenation, you check by some means of oxygenation parameters, PF ratio, how much PEEP they are requiring, is it decreasing, what is the pH? Patients are hemodynamically stable because you don't want to do it when the patients are norepinephrine of 50. So you want to have some assessment these patients are hemodynamically stable before you do weaning trial. Capability of initiating inspiratory effort, right? You will not do it on a paralyzed patient. So if I break it down into four criteria, so you are going to look at four different things before you will start the weaning trial. Assess readiness in terms of clinical criteria, ventilatory criteria, oxygenation, and pulmonary reserve. This is how I will summarize this for assessing readiness. So how do we assess readiness is step one, clinical criteria, what I'm going to look for. If the patient has ability to cough, clear their secretions, cardiovascular hemodynamically stable patients, and they have acute resolution of their disease, like as I said, if the COPD is resolving, ARDS is resolving, so you are looking at clinically at the bedside if the patient is getting better. You look at ventilatory criteria, is my patient able to ventilate, PCO2 is less than 50, pH is in a reasonable range, has a good vital capacity, minute ventilation is less than 10 liters, RSBI, frequency over tidal volume, less than 100, putting it all together that my patient can ventilate on its own. Oxygenation, again, PF ratio, PA2 with PEEP more than 60 at FIO2 of 40%, if the PEEP is less than 8, then should be more than 100 at FIO2 of 40. Oxygen saturation more than 90% at FIO2 of 40%, less shunt fraction, and AA gradient of less than 350 mmHg, so again, looking at my patient can oxygenate himself or herself if I take this tube out. Pulmonary reserve has a good pulmonary function, vital capacity more than 10 ml per kg, maximum inspiratory pressure is not too high, more than less, minus 30 cm of water, bed space less than 60%. Once I clear out that, my checklist in my head that my patient is ready, then I'm going to look for, is this patient safe for weaning trial? So how do you assess safety and how do you do weaning trial? We get spontaneous awakening trials and spontaneous breathing trials. I think all of us are doing it based on what we have learned from the literature. So a randomized control trial was done looking at how SAT and SBT coordinated effect helps in assessing patients for weaning. Was done in four tertiary care hospitals, 336 mechanically ventilated patients were randomly assigned to two groups, SAT followed by SBT versus patient on usual sedation undergoing SBT trial. Primary endpoint was time breathing without assistance, so basically how long the patient can last, extubation when we do either SAT plus SBT together versus just SBT. So results were very positive. The patients in the blue on the top are the SAT plus SBT patients. They spent more days breathing without assistance after extubation. They had earlier discharge from ICU. They also had earlier discharge from the hospital. So hence, SAT plus SBT coordinated trials should be done when we are doing weaning. We'll not spend too much time, but I'll just say it. Before we do SAT, SBT, we should make sure this patient is safe for us to do that. Many hospitals based on agency of healthcare research and quality have modified the protocol what works for their hospitals. For example, the Vanderbilt Hospital said, what is SAT safety? What is the safety screen? If we think through who are the patients whom I can wake up? The patients who have no active seizures, who are not under alcohol withdrawal, because those are the patients I will not wake up from sedation right away, right? No agitation, no paralysis, no myocardial ischemia. So once they hit that safety list, we go for spontaneous awakening trial. So spontaneous awakening trial, if they fail, then you resume sedation at half the dose and go back to and reassess the patient again tomorrow. If the patient does do pass the safety screen, you go for spontaneous breathing trial. Again, the spontaneous breathing trial safety would be if the patient can initiate a breath. You don't, I mean, of course our ventilators have backup plan, but again, you assess if the patient can breathe on their own. There is no agitation. Oxygen saturation is great. You are not going to de-recruit the patient once you do the SPT, and then you go ahead with the SPT. So if I have to summarize, you do all this pre-check assessment, you do a safety screen. Once they pass the safety screen, you determine the method of spontaneous breathing trial, you do spontaneous awakening trial, and you are ready to go for spontaneous breathing trial. The talk for today is how to do spontaneous breathing trial. Multiple methods. Here we are going to talk mainly about two because there's enough literature and growing literature on two methods. So the first one is pressure support. Ventilator delivers predetermined level of positive pressure each time patient takes a breath. Flow, inspiratory time, respiratory rate are all determined by the patient. The only thing we determine is when to cycle off the flow, which you can change 15 to 25 percent of the peak flow when you cycle it off. So basically, patient is initiating a breath. How we normally do it, we provide some pressure support, some PEEP, PEEP or no PEEP, but why we apply, provide some pressure support in order to overcome the tube resistance. And this is a guideline from ACCP and ATS in 2017, saying if patients are acutely hospitalized with critical illness for more than 24 hours, initial SPT should be conducted with inspiratory pressure augmentation, provide some inspiratory support, five to eight centimeters of water, rather than not providing support. For example, the way we do it with TPS trial or a CPAP. These are the other modalities how we can do spontaneous breathing trial. So based off of this recommendation, this is most of us do pressure support ventilation or pressure support trial for weaning. The recommendation strength is conditional and it is based on moderate quality evidence in 2017. The second what we are going to talk is spontaneous breathing trial by TPS, where the oxygen is delivered to the ED tube through a TPS, patient is disconnected from the ventilator. We are going to talk three trials on pressure support versus TPS. The first one published in JAMA was a randomized control trial done in Spain in 18 ICUs. Patients were randomized to either 30 minute of pressure support ventilation or two hours of TPS trial. So thinking that pressure support ventilation is less demanding, imagine, because we are providing some support to overcome the tube resistance. TPS trial, we are not providing that support, so this is a little bit more intense. So done for two hours. The primary outcome was to look at successful extubation, which is defined as remaining free of mechanical ventilation, basically no reintubation in next 72 hours after first spontaneous breathing trial attempt. So the results were very positive from this, saying the patients who underwent pressure support ventilation, they were having more success in staying extubated. But what we need to consider from this trial is, it was performed for 30 minutes for pressure support, but the TPS was done for two hours. Great trial, we were happy with it, but what the question arose is, do these findings apply to patients who are deemed high risk for extubation failure? Can we apply this to patients who have high risk of extubation? So in order to do that, another trial was done. So this is multi-label open, multi-centered open-label trial done in France on 969 patients. Again, randomized to 484 to pressure support and 485 to TPS trial, but at this time done in patients who have high risk of extubation failure. That is age more than 65 or patients have some kind of cardiopulmonary disease. Could be COPD, could be PH, could be left-sided heart failure, right-sided heart failure. So those are the patient population where this trial was done. Another thing to notice is here the TPS trial was done for one hour and the pressure support trial was done with pressure support of eight and PEEP of zero. In the previous trial, the pressure support was done at five and PEEP of five. Also, this trial, there was no limitation if the patient is struggling. Actually, it was recommended or encouraged that after extubation, if your patient needs non-invasive ventilation or high flow, sorry, not high flow, through oxygen mask. So if your patient needs non-invasive ventilation through a face mask for at least 48 hours or, sorry, or a high flow between the session, it's encouraged. So that means there were patients in this trial who after extubation went on to either high flow or face mask. Now we are interpreting the results. By saying that, there was no difference. Primary outcome was looking at total time alive and without exposure to invasive mechanical ventilation. There was no difference in the groups who underwent pressure support ventilation versus TPS trial. There was a signal a little bit, like, little difference. Pressure support, 97% of patients were extubated within seven days of initial SPT. But we are talking about within seven days, so I do not know if the first trial affected seven days difference. But overall, you can see 78% of the patients in both groups used non-invasive ventilation, 40% on both groups used high flow nasal cannula. So it's very hard to interpret this trial's efficacy that is pressure support not better or is TPS better. So it's an equivocal trial but with a lot of limitations. So the next trial which is being done, not published yet, attempt was now we need to look at patients who are at high risk of free intubation. We saw high risk of extubation failure but patients who are at high risk of free intubation to compare those patients with between pressure support and TPS. So more to come on that soon. Few things I want to talk about both is a work of breathing. So studies were done to see if the work of breathing between different type of spontaneous breathing trials is different. Pressure support, TPS, tube compensation or multiple ways how we beam the patients. Is there a difference in work of breathing between one mode versus another? It's a systematic review of 16 study and a pooled analysis was done on patients who were reflecting respiratory effort between studies. So the studies looked at respiratory effort of these patients by multiple means and then did a meta analysis on that systematic review of 16 studies. What it showed is if you can see on the top the work of breathing favors pressure support ventilation over TPS trial all across the board. So the signal is when you put patient on pressure support ventilation their work of breathing is less as compared to any other mode. Specifically here in this study comparison is done with TPS trial. Similarly pressure time product which is another marker of how patient is initiating a breath or what is the work of breathing in this patient is also low in in pressure support ventilation. That means when you put patients on pressure support ventilation they do less work of breathing. It imposes less work of breathing to them. Does that correlate? How does that correlate to extubation? Is it if the patients are doing less work they will have more extubation failure or they will be extubated early? So another way to look at it they also looked at pressure support versus pressure support of zero and CPAP of zero. Again it favored pressure support. So what they concluded is that pressure support patients can be extubated early on because they don't have to do much work of breathing. They don't tire out because we are not putting them under too much stress. But if the patient is at a high risk of reintubation in those patients maybe you want to do a stressful test, more stress test like stress echo is a TPS trial to see if they fail TPS. That means they have a more reintubation, they have more chances of getting reintubated. Comparing lung aeration. So lung aeration, lung aeration with any spontaneous breathing trial decreases. But the question is even after extubation it decreases so it doesn't matter. So if you are looking at lung aeration or lung expansion on pressure on breathing trials they will happen but between pressure support and between TPS trial post extubation the lung aeration was decreased to the same extent. Duration of SPT is another concept. I'll just go through this one thing. Pressure support of 30 minutes is rate of success in SPT is best when you do pressure support of 30 minutes. It's more than pressure support of 120 minutes, more than TPS of 30 minutes, and more than TPS of 120 minutes. Coming to the same conclusion that pressure support of 30 minutes had a higher rate of success for extubation but TPS of 120 or pressure support of 120 longer duration has better success in predicting outcomes in reintubation. So shorter the trials, more chances of success in extubation. Longer the trials you are trying to see if this patient is at risk of reintubation and should I be extubating this patient. Okay another thing in a POCUS area now you can use diaphragmatic exertion and diaphragmatic thickness fraction as the surrogate of RSBI to predict veening. I just put it in because this study came out the last on the veening trial. Multiple other studies are in features. If you see there is a PAV, there is automated tube compensation, smart care, all these studies are being studied. I mean all these modalities are being studies as successful means of veening trials. But there is not enough data, there is no much generalizability, more studies needs to be done on those modalities. At this moment we go by pressure support versus TPS. Pressure support more for extubation, TPS more when we are risking this patient for reintubation. Sometimes we do TPS more on those patients. Key takeaways, protocolized veening strategies reduces duration of mechanical ventilation. Coordinated SAT SBT have better outcomes. SBTs with pressure trials results in higher rates of successful extubation. No difference in patients with high risk of extubation failure. Work of breathing is lower with pressure support. Pressure support 30 or 120 minute have a higher rate of success in extubation. But TPS trials have higher chances of predicting reintubation. Thank you. So my name is Deedee Gardner. I understand if you need to run away we have about five, seven minutes to go through a 15 minute presentation. So just bear with me but I'll try to run through it as quick as I can. My real job is I'm the Chief Research Officer for the Allergy Asthma Network and we're going to fly through the intubation strategies for describing the role of high flow and non-invasive ventilation in the prevention of reintubation. We know that extubation failure is reintubation secondary to post-extubation respiratory failure. The time frame is between 48 hours and seven days and this occurs ideally in between 10 to 23 and a half percent of people according to the guidelines from ERS. There's a number of patient risk factors that we need to be concerned about and so the previous presenters have talked to you about those but make sure that when you are thinking about extubating a patient that when you're looking at risk factors if there's two or more of these listed up here then that that's going to let you know that you probably have patients who are at high risk and then there's some studies that we'll look at here in just a second looking at very high risk. It's extremely important to also consider comorbidities and then also in regards to patients being having the ability to clear their airway. If they can't clear their airway then it's most likely that they'll probably end up being reintubated. So Hernandez and all looked at reintubation and also looking at something referred to as high risk very high risk patients and that was taking four of those risk factors that you saw previously. They did a randomized control trial looking at non-invasive and high flow nasal cannulas for 48 hours after extubation. They were really looking to see if anybody was reintubated within seven days after the extubation and found that out of the 182 patients they randomized them into two groups, 90 of them into the high flow group and 92 into the non-invasive group and found that 23% of those in non-invasive and 38% of those in high flow were actually reintubated. Trying to figure this out what they discovered is that with anyone who had four risk factors those were really the patients that ended up being reintubated. Also those patients were the ones that responded better to non-invasive ventilation than anyone else. There is a the ERS does have a clinical practice guideline that was published in 2022. They only have one of their PICO questions that was focused on non-invasive and high flow nasal cannula. The literature that was supporting of this was conditional recommendation with moderate evidence so that lets us know that there is research out there as of 2022 that did support non-invasive over high flow when you're looking at extubating patients who are at high risk for extubation failure unless there's an absolute contraindication. So if we're looking at early non-invasive after planned extubation meaning that as soon as you extubate the patient you put them on non-invasive at certain settings then that will decrease the rate of needing to be reintubated and also mortality. So if we're looking at high flow the literature that supported this was that high flow basically just improved patient comfort and also that it limited the risk of non-invasive related adverse events. The patients did better tolerate the high flow nasal cannula than they did the non-invasive ventilator. When we're looking at systematic and meta-analysis reviews in 2023 there was a group referred to as the Balsco et al. This was in the European respiratory review. They looked at a randomized controlled trial of non-invasive support and that was with CPAP and BiPAP compared to high flow nasal cannula. And they looked also at the high-risk patients but this inclusion criteria was only those that were greater than 65 who had heart disease, pulmonary, or respiratory disease. Not any of the other high-risk categories that we saw previously. So here what we find is that those that were on or utilizing high flow nasal cannula overall benefited and those that were utilizing non-invasive benefited. So anyone over the traditional oxygen therapy as when Dr. Casey was talking earlier traditional nasal cannula type of therapy really is not the answer here. We really need to be putting in pressure with non-invasive or high flow because the goal is to oxygenate the patient. So high flow nasal cannula in this in this study actually reduced extubation failures compared to the traditional conventional oxygen therapy. However with some group analyses they did find that if you were prophylactically placing a patient on non-invasive, meaning that you put them on as soon as you've extubated them, not that you waited for them to start having signs and symptoms, that we actually reduced the rate of extubation failure in those patients. That was 12 studies in 1,700 people so that definitely gives us some credibility. However neither prophylactic nor non-invasive reduced the rate of extubation in low-risk patients. So anyone who actually is younger maybe does not have underlying comorbidity and that was with 1,400 patients. Continuing with when we're thinking about the ERS guideline and this systematic meta-analysis, what we found is that there is some congruence in regards to using non-invasive to reduce the post-extubation respiratory failure only in non-surgical patients. However in those patients that were not were post-operative and had post-operative respiratory complications there's a discordance between the ERS guidelines and this systematic review. Fernando and et al looked also at a systematic review of meta-analysis and they looked at over 36 randomized control trials with 6,000 people, almost 7,000 people in those, and they compared the again the traditional oxygen therapy with non-invasive and high flow and they also found that either one of those would reduce the reintubation issues. On this slide here what we're looking at is non-invasive and conventional. We find that there is positive outcomes. Also high flow by itself compared to conventional has positive outcomes. However non-invasive versus high flow there is not enough evidence. High flow versus high flow alternating with non-invasive compared to conventional there is good evidence and then high flow by itself or non-invasive by itself really there's not a lot of evidence when you're looking at high flow plus non-invasive. So the take-home is use one or the other but not conventional therapy. So when we're thinking about evaluating our patients to prevent reintubation this is a different systematic review by Wang. They looked at 13 studies and they had six studies that were in English and seven that were in Chinese. There was no significant difference between either one of the mechanisms to prevent intubation. So extubation failure. We do know that there are concerns if we are losing a patient to extubation failure because of mortality. 50% of patients do die once they are extubated. There's poor prognosis. There's a lead to having the patient have prolonged mechanical ventilation here in the U.S. There's also high risk of all of these wonderful side effects such as ventilator associated pneumonia weakness and delirium and then we also see that our health care costs are increasing. So in the future what we need to look for is that we establish a definition for extubation failure that we have a consistent high risk factors that we're looking for in the studies that were that are being contributed to the literature. That we consider the thought of having high risk patients versus very high risk patients in the nomenclature that we're using. And then future studies we really need to this is not something that we really got into at all today but there are some different nomenclatures when we think about high flow nasal oxygen that we also have insufflation depending on your definition there and so just depending on what device you're looking looking at and then also the settings for each of these devices. Every study had a different setting. Some used 50 liters per minute. Some used 60 liters per minute. The non-invasive pressures were different across all studies. None were consistent and so it's hard to compare all of them and say that one is better than the other. The last thing that I would say is that when you're developing studies is to make sure that patients who have experienced these devices are involved in the studies because your outcomes will be much better. So thank you.

intubation

extubation

reintubation

critically ill patients

hypoxemia

pre-oxygenation

high-flow nasal cannula

non-invasive ventilation

spontaneous breathing trials

patient risk factors