Thank you very much. Thank you to SCCM for the invitation. So I'm going to talk to you about other aspects of extubation considerations that are beyond the SBT. So SBT, in my view, is like a rehearsal for a big orchestra. And ventilator liberation, we know, is an orchestra performance because every instrument has to play on time and play perfectly. Otherwise, you have extubation failure. So what are the other features or factors? Just quickly, my disclosures, I have some clinical trial funding and I was on the panel that developed these guidelines, but no other relevant disclosures. So I'm going to cover three key factors that are additional to the SBT. And I think Samer is going to talk about upper airway obstruction after me. So one of them is respiratory muscle strength, which is obviously closely linked to SBT performance, but can delve a little bit more into detail on that. The second is obviously the level of sedation, neurology, neurological status and airway maintenance and secretion clearance, which are all kind of tied in together. And the third is about post-extubation respiratory support, mainly a planned initiation of respiratory support post-extubation. So you saw earlier that this is the guidelines document that was produced by the panel and was published earlier last year. And it goes through several recommendations for all the PICO questions. So just looking specifically at the respiratory muscle strength assessment, as part of the systematic review process and the consensus approach, we looked at a few factors that might influence the respiratory muscle strength. So PI max and other similar features of respiratory muscle strength, so P0.1, et cetera. We looked at the diaphragmatic thickening, thickness fraction and electrical activity of the diaphragm. So these were the three main ones that we looked at as part of the literature review. Just to quickly summarize how the guidelines process worked and what the evidence there was, essentially a big fat zero in terms of the number of RCTs that were used or conducted comparing different respiratory muscle strength measures or indices to predict extubation failure. We had several observational studies as part of that systematic review that we identified, 19 of them at the time. So I can quickly go through what those 19 studies showed. They were mostly covering PI max or something similar. So essentially these are measurements that you do on the patients prior to extubation to assess their respiratory muscle strength. Seven studies on diaphragm thickness fraction. So this is difference between diaphragm thickness in inspiration and expiration. And prolonged ventilation obviously causes changes in the diaphragm thickness fraction. And then three studies on diaphragm electrical activity. For shortage of time, I'm not going to go into too much detail on the diaphragmatic assessments, but mainly focus on the PI max, which is what the guidelines focused quite a lot on. So just looking at the nine studies, the observational studies that looked at PI max and extubation outcomes, you can see that there were about 1,800 patients in these nine studies, observational studies. The extubation failure rates ranged from 8 to 22 percent. So lower risk of extubation failure as well as higher risk of extubation failure patients. And the pressures that were identified as thresholds ranged from 20 centimeters of water to 50 centimeters of water. So you can see here that at each of these thresholds there are different sensitivities and specificities to predict extubation failure. I suppose the bottom line here is that there is a huge range of pressures, thresholds and sensitivities and specificities that make it quite difficult to try and put it all together and give a very clear recommendation. But this was the recommendation that we came up with. That inpatients who are at risk of extubation failure or higher risk of extubation failure or have muscle weakness. So these are the targeted patients who have a higher risk of respiratory muscle weakness that using PIMAX as one of the measures of respiratory muscle strength as part of the ERT bundle for critically ill children was recommended. But you can see it was a conditional recommendation with very low certainty of evidence, no RCT evidence for sure. And the thresholds that were identified from the table were if you had a very low PIMAX, then it means you had a higher risk of increased risk of extubation failure because you were weak. And if you had a high number, it means you had preserved muscle strength and you would likely succeed the extubation process. And I think those are suggested thresholds, but there is no magic number from the studies. So quickly skipping through to an assessment of sedation and airway management and airway secretion clearance. Again, no RCTs that focused specifically on the peri-extubation period. But there were two RCTs that looked at sedation management or protocolized sedation management during the entire process of invasive mechanical ventilation, including up to the part that patients were extubated. So not specifically looking at just the peri-extubation period, but looking at the entire process. And those two trials, I'm sure you know, are from Martha Curley and Bronagh Blackwood from Belfast. So the sandwich trial published recently in 2021, a protocolized sedation and ventilation liberation protocol. And the bottom line, if you look at continuous outcomes, such as a duration of NIV, mechanical ventilation duration, length of stay, and PQ length of stay, the protocolized sedation was better for most of those outcomes. And this is for the whole part of invasive mechanical ventilation. And for binary outcomes, dichotomous outcomes, slightly more mixed picture, but protocolized sedations were better for some outcomes. So I think overall, probably the conclusion would be that we would want to use some kind of protocolized sedation. Methods doesn't necessarily say which one to try and keep patients optimally awake at the time of the extubation, obviously. There were two recommendations, 13 and 14, which were not evidence-based, mostly good practice statements. So first of all, to say that level of sedation, cough effectiveness, and capacity to manage secretions should be tested before extubation. That wasn't necessarily based on any of the studies because there wasn't really that much evidence and it was fully consensus-based. So more than 80% agreed that this was sensible. Also targeted sedation management strategy. And then the recommendation that came from the data was that a standardized sedation titration protocol might be used. But equally, there was no real strength to say that not using a protocol was not appropriate. So I think it leaves the choice, as Alex pointed out, some of these recommendations quite hedged in terms of what they suggested. Finally, just looking at post-extubation respiratory support, two questions were addressed. One was timing. So would we start patients who are about to be extubated on planned initiation before you test whether they are okay after extubation? Or would you just extubate them and rescue them with non-invasive support? And the type of respiratory support that you would use. Is it high-flow nasal cannula? Is it CPAP? Is it BiPAP? Is it other forms of non-invasive now, like negative pressure ventilation? So this is the PRISMA chart from the systematic review that was carried out as part of the guidelines. There were two randomized trials that compared high-flow with CPAP, total of 632 patients. Five randomized trials that compared any form of non-invasive respiratory support with conventional oxygen therapy. And the smaller numbers, about 470 patients. Just quickly looking at the type of non-invasive respiratory support, there were two trials. Both were our group, the first ABC pilot trial and the first ABC definitive trial, which showed that you can see that CPAP was shown overall to be more beneficial across the patient population. This was particularly obvious in the under one patient population. And a network meta-analysis which was carried out as part of the guidelines process showed, as you can see at the bottom, that the odds ratio of extubation failure was lower with CPAP or NIV compared to high-flow nasal cannula therapy. So you can see the odds ratios there. And that was clarified further in this recent publication in JAMA Pediatrics which came out of the guidelines group, which showed that the area under the, the surface under the cumulative response curve, the sucra, was highest for CPAP. So you can see that for extubation failure as well as for treatment failure, so that's any form of escalation required after extubation, both of them, CPAP was, sort of had a higher sucra than high-flow nasal cannula therapy. So summarizing that recommendation from the guidelines, again, the focus was on children at high risk of extubation failure. The use of non-invasive support, which could be any of those three forms, high-flow CPAP or NIV, was advised over just conventional oxygen therapy. So I suppose what that means is that for high-risk patients, planned initiation of one of those modes was recommended. And patients who were infants under the age of one, when they were being started on either planned or rescue forms of non-invasive support, that CPAP was preferred over high-flow nasal cannula therapy. So thank you very much to the Ventilation Liberation Panel. I was part of this, as were many others here. And thank you particularly to Samer and Robbie for their leadership. Thank you.

extubation strategies

respiratory muscle strength

non-invasive respiratory support

protocolized sedation

randomized controlled trials