Thank you so much, Dr. Barr. The blessing and curse of being 6'2". So welcome to Part B of Resuscitating the Bundle, both spontaneous awakening and spontaneous breathing trials. As mentioned, I'm Neil Prendergast. I'm a former critical care physician at the University of Pittsburgh, and I have the honor of leading an approximately 15-minute tour of the path the field has taken over the last really 60 years, and where I hope that path will lead. I should always start with I have no financial conflicts to disclose. So as part of that line, we'll start with how ICU practice came to be, particular practice regarding sedation and weaning from mechanical ventilation. We'll follow two parallel through lines, breathing and awakening, essentially from the birth of critical care medicine to now. We'll continue to current best practices and the reality on the ground, both immediately prior to and during the COVID pandemic. And finally, we'll conclude with a glimpse into the future, or perhaps better said into several possible futures. A few notes before we get started, I have structured this as a narrative review using several seminal trials as signposts, and I probably will overgeneralize when I say that the field did X. What I mean is that X became more common. So where have we been, and how did we get here? It would be reasonable to start a discussion of critical care practice in 2000 BC, when the first tracheotomy was described, but for our purposes, we'll start in the 1960s. That was when intensive care units were becoming more common at major centers in the United States and worldwide. And in particular, I'd like to start at Colorado, with the respiratory intensive care unit that was led by Tom Petty for a number of years. This unit's particularly useful for our purposes, because it was set up as a respiratory intensive care unit, and so weaning from mechanical ventilation was in the forefront of the minds of leadership, because the use of sedative hypnotic agents was rare, and because they wrote down their practices. When thinking about extubation, liberation from mechanical ventilation, everywhere was doing something a little bit different. And the group at Colorado, in search of more objective measures, performed a trial, which Dr. Petty then included in a review of their first 10 years of practice. You can see the criteria on the screen. The patient has a resting minute ventilation of less than 10 liters, can double that ventilation or that volume on command, and can generate an instantaneous negative pressure of minus 30. That patient is very likely to be able to be extubated. And this turned out to be true. All 76 such patients were extubated without any reintubations, although these criteria were not necessarily the most sensitive. They left 7 of 24 on the table. So this is the first step to protocolized liberation, but it's not really a weaning protocol. And over the next 20 years, there were multiple efforts, both on the part of critical care medicine as a discipline, and on the part of ventilator companies, to smooth the weaning process with spontaneous or mandatory ventilation and pressure support ventilation in particular. However, ventilator weaning remained largely empiric until about 1995. At that time, Andres Esteban and colleagues published a paper examining 130 patients who had had respiratory distress during an initial weaning attempt. They randomized those patients to one of four techniques, either intermittent mandatory ventilation with slow decreases in the respiratory rate, pressure support ventilation with slow decreases in the support pressure, or intermittent breathing trials, either once or more than once per day. And it was found, as you can see, that a once-daily spontaneous breathing trial was associated with a nearly three-fold higher rate of liberation compared to intermittent ventilation and more than twice the rate of pressure support ventilation. And this really ushers in the era of the spontaneous breathing trial. And to this, the next year actually, Wes Ely and colleagues at Vanderbilt published a paper looking at basically how you decide when to start. And they randomized patients to either screening and an SBT conducted by the research staff with the results then communicated to the treating team or to screening alone. And similarly, as you're all aware, they found a significant difference. Patients got off the ventilator a day and a half faster in the intervention compared to the control group. Interestingly, counter to some fears, but consistent with the bulk of subsequent literature, the risk of reintubation was actually higher in the control group. You can get people off both more safely and more quickly. And so at this point, by the mid-1990s, the field has established that spontaneous breathing trials are beneficial. And there's still work to do, particularly in how one performs an SBT. But for the moment, I'd actually like to switch to our other through line, awakening. As Dr. Barr mentioned, in between the 1960s and the 1990s, the practice of deep sedation was increasingly, and by mid-1990s, overwhelmingly common. A major driver was, obviously, the increased use of sedation, particularly continuous intravenous sedation. And that's shown very nicely from this figure, or by this figure, from a 1998 paper by Maren Koloff and colleagues examining practice at Barnes-Jewish Hospital in St. Louis. Here they took patients who were receiving continuous intravenous sedation, comparing them to those who weren't. And even after matching the cock proportional hazards model for obvious covariates, they found a marked difference in the duration of mechanical ventilation, on the order of five days on average, between those patient groups. And I include this both because it's bad, but because also it is indicative of the practice environment at the time, a fact which was bemoaned, actually, by one Tom Petty, in the editorial that accompanied this paper. And I'll read you just a selection of his words from that editorial. What I see these days are paralyzed, sedated patients, lying without motion, appearing to be dead, except for the monitors that tell me otherwise. Why this syndrome of sedation and paralysis has emerged baffles me, because this was not the case in the past. Now, who here has flashbacks to mid-2020? The field obviously recognized this was a problem and began to move back from that high or low water mark, depending on how you think about it, starting in 2000. In 2000, J.P. Kress at the University of Chicago published a paper examining a daily sedation interruption as a way of minimizing sedative exposure in mechanically ventilated ICU patients. And the daily sedation interruption, later known as the spontaneous awakening trial, was simply that. Once a day, you turned everything off. The research staff would then assess the patient, and when the patient was awake, contact the patient's treating team. No other decisions were made. Despite that, patients were liberated from mechanical ventilation much more quickly, nearly two and a half days more quickly. These two approaches, spontaneous breathing and spontaneous awakening, were then combined in the Awakening Breathing Controlled trial, or ABC trial, published in 2008. Here, patients were randomized to either a combination of spontaneous awakening, that is sedation interruption, and spontaneous breathing trials, or simply spontaneous breathing trials alone, as that had become standard care. And even so, patients had just over three more ventilator-free days with the combination of SAT and SPT, compared to the usual care of SPT alone. And so, as almost counterintuitive as it is, by 2008, the field had realized that this was necessary, that this was best practice. And so, in some sense, we were, 15 years ago, where we are now. In those 15 years, still a lot of work has been done, and I'll go over a little bit of that before I turn to the pandemic. Much of the work on spontaneous breathing trials has focused on how to do a spontaneous breathing trial. And so, for example, do you use pressure support or TPS? How long? This is a figure from a 2019 trial, comparing, in essence, a more demanding to a less demanding SPT. So, a more demanding, a two-hour TPS trial, versus a less demanding, half-hour pressure support trial. And this trial found, has a ratio of about 1.5 in favor of the pressure support trials. Similarly, but not exactly the same, was a more recent trial published just last year, comparing roughly one-hour pressure support to roughly one-hour TPS trials in high-risk patients, that is, over 65 or with pre-existing heart or lung disease. And this study did not find a significant difference, although some secondary outcomes favored pressure support. So as a result, best practice is an SPT, probably a pressure support SPT, but no one will fault you if you use TPS or CPAP. Inquiry into spontaneous awakening trials is mostly focused on implementation. And one example is this before-after study from Heidelberg in Germany, showing that the implementation of an SAT and SPT protocol led to a nearly 20% increase in successful estimation rate. Even so, despite good consensus that this is best practice, it wasn't universal. And this is just a reformatting of data that Dr. Barr showed, showing essentially that SATs and SPTs were performed approximately by two-thirds of physicians in the immediate pre-COVID era. Obviously, the COVID era was not kind to these practices. And so these are data similar to, but not the same as those shown by Dr. Barr. This is a worldwide survey of physicians actually focusing on non-American physicians. You can see that physicians were much more likely to prescribe sedation to mechanically ventilated patients and were more likely to use continuous sedation without a daily interruption. And these changes arose likely from a place of beneficence. Physicians were confronted with an epidemic of viral ARDS, and the tools available, particularly early in the pandemic, were proning, paralysis, and extracorporeal support, all of which necessitated or at least strongly indicated deep sedation and no ventilator liberation. Still, as previously presented, this has not been benign. Post-intensive care syndrome has become much more common. And so the question remains, where are we going? I presented, in essence, a history lesson because the COVID pandemic has in some ways been the history of critical care in microcosm. We began not sedating people much, getting them off the ventilator relatively quickly. And over time, we began to sedate people more deeply, more heavily, and keep them on the ventilator much longer. There are two possibilities. One is that COVID is special and that our practices need to be reexamined. But much more likely is that it's not. And that what we should be doing in the future is what we have been doing in the past. Obviously, this figure should look very familiar. Not just spontaneous awakening, spontaneous breathing trials, but the whole ABCDF bundle are critical to removing patients from mechanical ventilation, minimizing coma and delirium, minimizing the use of physical restraints, and improving ICU outcomes. Thank you very much for your attention. And I'll be happy to take questions.

spontaneous awakening

breathing trials

critical care medicine

mechanical ventilation

sedation practices