Hello, everyone. This is Timothy Gerard from the University of Pittsburgh, and I want to thank you for this opportunity to share with you my presentation, Successful Weaning and Extubation for SCCM 2022. Before we get started, I have a few disclosures. First, I receive research funding from the National Institutes of Health and from Cerebel. I've consulted for Haseco Pharmaceutical, and I'm on the advisory board for Lungpacer Medical. 20 minutes isn't really a lot of time to cover all of the evidence regarding liberation from mechanical ventilation, so what I decided to do for today's presentation is to focus on four of the questions that were addressed in the 2017 ATS-ACCP joint clinical practice guidelines on liberation from mechanical ventilation. There were six questions that were addressed in these guidelines, but these four are most directly relevant to today's presentation. So I'll be discussing the evidence on ventilator liberation protocols, as well as on the use of pressure augmentation during SBTs or spontaneous breathing trials. I'll discuss what we know about the value of cuff leak tests and when to use them prior to extubation, and then finally on when to use preventive post-extubation non-invasive ventilation. I'll start by reviewing the clinical trial data supporting the use of ventilator liberation protocols, but before I move ahead, I want to point out that all of the evidence discussed today assumes that the spontaneous breathing trial is the focal point of your liberation strategy. These are based on data that were reviewed during an early clinical practice guidelines, published all the way back in 2001, during which they recommended, based on clinical trials, a spontaneous breathing trial, whether then another strategy such as an SIMV wean or a pressure support wean, as the main strategy by which to determine patients who are ready for liberation from mechanical ventilation. So with that assumption that you are using spontaneous breathing trials as your liberation strategy, the 2017 clinical practice guidelines ask this question, should acutely hospitalized adults who have been mechanically ventilated for more than 24 hours be managed with a ventilator liberation protocol or with no protocol? The systematic review conducted for these clinical practice guidelines found that eight randomized controlled trials evaluated this question of liberation protocols, but I'm going to highlight for you one of these trials before showing you the evidence summarized for all eight trials. This specific trial was conducted by Wes Ely and colleagues at Wake Forest, and they randomized patients to either a control strategy, which consisted of physician-directed liberation or weaning, versus a protocolized strategy during which respiratory therapy providers implemented a SBT protocol. Now the physicians who determined how patients were liberated in the control strategy also were able to use spontaneous breathing trial or whatever approach they thought was best for each individual patient, but the respiratory therapy providers and the protocolized group were all using a spontaneous breathing trial protocol that first evaluated the patient's readiness to even undergo a spontaneous breathing trial, so-called safety screen, and then second, the spontaneous breathing trial itself. If the patient passed the trial in the protocolized group, the decision to extubate was not made as part of the protocol, but instead was made by the physicians caring for that patient on that day. As you can see here, overall patients who were randomized and managed with the protocol were extubated earlier than patients in the control group and spent significantly less time on mechanical ventilation. When you examine the data from Ely's trial as well as seven other trials in a meta-analysis, you find that the weight of the evidence indicates that liberation protocols are better than using no protocol as measured by a reduction in duration of mechanical ventilation as well as improvements in other related outcomes. Based on these data, the clinical practice guidelines do recommend using liberation protocols when managing mechanically ventilated patients who are being treated for acute respiratory failure in an ICU, but acknowledge that this is low-quality evidence primarily because the trials are unblinded, which you'll find is a very consistent limitation for all of the clinical trials that examine strategies that improve or seek to improve liberation from mechanical ventilation, and then also because of inconsistent results. There was also notably insufficient evidence to recommend one protocol over the other, and I want to specifically highlight that some of the more recent clinical trials in this area have examined computerized protocols rather than respiratory therapy-driven protocols, and it's not clear at this current time whether computerized protocols are better than respiratory therapy-driven protocols. What is clear, however, is that using a protocol is better than not using a protocol. The next intervention I'll discuss is the use of pressure augmentation during a spontaneous breathing trial. This is commonly done by applying inspiratory pressure with the patient connected to the ventilator in a pressure support mode, and this is in contrast to the traditional approach of using T-tube or T-piece during a spontaneous breathing trial, or even keeping the patient connected to the ventilator but just using PEEP or CPAP rather than an increased pressure during the inspiratory phase. The specific question addressed in the clinical practice guidelines is, in acute hospitalized patients ventilated more than 24 hours, should the spontaneous breathing trial be conducted with or without inspiratory pressure augmentation? One of the largest clinical trials that compared a strategy using inspiratory pressure during an SPT with an SPT that did not use inspiratory pressure, in this case T-piece, was actually conducted and published after the clinical practice guidelines that I'm reviewing today were prepared. And for that reason, I wanted to highlight this trial. In this clinical trial, a 30-minute pressure support SPT was compared with a two-hour T-piece SPT. So it wasn't just the use of inspiratory pressure during the SPT, but also the duration of the SPT that was compared and it's impossible to really sort out the relative effect of those two details. So in summary, I would describe this as a lower threshold SPT, shorter with inspiratory pressure, versus a higher threshold or more strenuous SPT that was longer on T-piece. And in this clinical trial, what they found was that patients who were assessed with the shorter, easier SPT were extubated more quickly than patients who were assessed with the longer SPT. And that was a persistent difference. It was not made up for later by a different re-intubation rate. In other words, patients were more likely to be successful and to remain successful if they were assessed with 30-minute pressure support SPT than with a longer T-piece SPT. These results are consistent with those of earlier trials, which were analyzed in the meta-analysis for the ATS-ACCP clinical practice guidelines. There were three trials that were applicable to this question regarding pressure augmentation, and those three trials consistently favored SPT with pressure support. And when analyzed together in this meta-analysis, it had a significant difference in SPT success in favor of the use of inspiratory pressure during spontaneous breathing trials. Now, I should point out that none of these trials used more than 7 centimeters of water inspiratory pressure, that is, 7 centimeters of water above PEEP during the inspiratory phase during an SPT. So it would not be considered an SPT, at least according to these clinical trials, if a patient was on, for example, 10 centimeters of water inspiratory pressure relative to their PEEP. So based on these data, the clinical practice guidelines recommend using pressure augmentation based on moderate quality evidence. The major reason that evidence wasn't higher quality was because the trials, as I mentioned earlier, were unblinded. And I should point out that these trials always examined only the first SPT. So we really don't know if the findings apply to patients who fail multiple SPTs and then finally pass one. Those patients weren't included in these clinical trials, at least not after their first SPT. We also should point out that most of the clinical trials that examined this question enrolled or recruited patients with ARDS or COPD. So it's possible that the results don't generalize to all types of patients with acute respiratory failure. The next question examined in these clinical practice guidelines was that of the use of the cuff leak test. So in this particular instance, we're talking about the point in time after which a patient has passed a spontaneous breathing trial. And the question now is whether or not it's appropriate to extubate them. It has been common for some clinicians in the past to use a cuff leak test in this instance to determine whether or not there's evidence that a patient has tracheal edema and or airway edema and therefore needs to be extubated after some interventions such as corticosteroids or after more time has passed to allow for that edema to abate. The clinical practice guidelines actually examined two related questions regarding cuff leak tests. First, should a cuff leak test be performed before extubation of mechanically ventilated adults? And second, should systemic steroids be administered to adults who fail a cuff leak test before extubation? And by fail a cuff leak test, what I mean is that the test suggested there was not a cuff leak and that there was tracheal or upper airway edema or swelling that was preventing the leakage of air when the cuff was deflated. It turned out that the systematic review was unable to identify any interventional trials testing the effect of cuff leak tests on clinical outcomes and therefore a two-armed simulated trial was created using data from observational studies. This trial compared the effect of a cuff leak test on two related outcomes, one being extubation success related to re-intubation and the other being the duration of mechanical ventilation. Because the identification of a patient who did not have a cuff leak would lead to more days of mechanical ventilation because their extubation would be delayed but also would reduce re-intubation for a certain proportion of patients who would have otherwise been extubated had the lack of a cuff leak not been identified. In summary, it was determined that cuff leak tests do in fact reduce the rate of re-intubation but they do so at the expense of adding days of mechanical ventilation for patients whose extubation is deferred and when you take the overall rate of re-intubation, even amongst patients without a cuff leak, it turns out that more patients have their duration of mechanical ventilation prolonged than there are patients who have re-intubation prevented. So in summary, when you put all of this data together, if you were to use cuff leak tests across all patients who are mechanically ventilated greater than 24 hours, the data, which are very low quality evidence for reasons that I've described, would suggest that a cuff leak should not be used for all patients. However, the cuff leak should be used to assess patients prior to extubation if those patients have specific risk factors for post-extubation stridor. These would include having had a traumatic intubation, being intubated for greater than six days, being female, having a large endotracheal tube, and having a re-intubation after an unplanned extubation. So in general, if a patient has multiple risk factors, the recommendation is to assess them with a cuff leak test prior to into extubation. But if they do not have multiple risk factors, then do not bother with using a cuff leak test. Now, I don't show you the evidence here, but if you do perform a cuff leak test and find that a patient does not have a cuff leak, then there are clinical trial evidence as reviewed in these clinical practice guidelines that suggests that systemic steroids would be helpful in that circumstance. And the guidelines do in fact recommend steroids be given to a patient who's high risk for post extubation stridor and who fails a cuff leak test, meaning they did not have evidence of a leak around the cuff. The last intervention I'll be reviewing today is that of preventive post-extubation non-invasive ventilation. And I specifically want to highlight this word preventive, because what I'm not talking about here is the use of non-invasive ventilation after extubation to rescue a patient who's having post-extubation respiratory failure. That approach with non-invasive ventilation has been studied in clinical trials and found to be not effective. Rather here, we're talking about a patient who passes a breathing trial, is extubated, but then because they have high risk features such as hypercapnic respiratory failure or chronic heart or lung disease, they're placed on non-invasive ventilation as a preventive or prophylactic measure for a period of time to reduce their risk of recurrent respiratory failure after a planned extubation. The question that was asked in these clinical practice guidelines is, in high risk patients receiving mechanical ventilation for more than 24 hours who have passed a spontaneous breathing trial, does extubation to preventive non-invasive ventilation compared with no non-invasive ventilation have a favorable effect on multiple patient-centered outcomes? I'm going to highlight one randomized controlled trial here conducted by Ferrer and colleagues and published in The Lancet in 2009 that specifically recruited high-risk patients, which they defined as patients with hypercapnic respiratory failure and found that those patients who were extubated to preventive non-invasive ventilation had lower overall mortality than those patients who were extubated to a control strategy, which in this trial was low flow or conventional oxygen therapy after extubation. There were four randomized controlled trials that met criteria to be included in the meta-analysis for these 2017 clinical practice guidelines, and these trials all found that the use of preventive post-extubation non-invasive ventilation tended to yield better outcomes than no non-invasive ventilation, and taken together, the overall evidence favored the use of non-invasive ventilation. Now, I should highlight here that in none of these trials was the control strategy post-extubation high flow nasal cannula oxygen. That's a strategy that's been studied more recently and was not examined in these particular clinical practice guidelines, but there have been recent meta-analyses published suggesting that high flow nasal cannula oxygen after extubation is also beneficial, as these trials have shown was the case for non-invasive ventilation. So in summary, the clinical practice guidelines recommended post-extubation non-invasive ventilation for prevention of respiratory failure in patients at high risk, and that was based on moderate quality evidence, again downgraded because of unblinding in these clinical trials, and they specifically defined high risk in the clinical practice guidelines as patients who either have hypercapnic respiratory failure or have chronic lung disease, most often COPD, or chronic heart failure. The use of non-invasive ventilation, as I pointed out, should be delivered immediately after extubation rather than waiting for respiratory failure to occur, and using it preventively leads to good outcomes, but using it as a rescue therapy has not been shown to be beneficial in clinical trials. And as I mentioned, high flow nasal cannula oxygen may be equivalent. That's still a question that hasn't been clearly answered in clinical trials. So in summary, the clinical trial evidence favors the use of ventilator liberation protocols and pressure augmentation during spontaneous breathing trials, as well as preventive post-extubation non-invasive ventilation in high-risk patients, but does not suggest that cuff leak tests should be used in all patients, but instead should be focused specifically on patients with multiple risk factors. Thank you for your attention.

weaning

extubation

ventilator liberation protocols

pressure augmentation

cuff leak tests

preventive non-invasive ventilation