#476 - Does NIPPV Work or Is It Just Higher Mean Airway Pressure?

Hello friends 👋

Dr. Brett Manley joins Ben for the opening episode of The Incubator’s special series on non-invasive ventilation, recorded ahead of Hot Topics in Neonatology. They work through the full arc of non-invasive support, from the delivery room to the convalescent phase and beyond. What actually counts as nasal high flow, and when should it come off? Why did HIPSTER and HUNTER move clinicians back toward CPAP as primary support? Is the benefit of NIPPV about synchronization or simply higher mean airway pressure? Brett shares his own weaning approach, the ÉCLAT findings, and the trials he believes the field needs next.

This series is produced in partnership with Hot Topics in Neonatology and Fisher & Paykel Healthcare.

Join us at Hot Topics in Neonatology: National Harbor, MD, December 6 to 9, 2026. Register here: https://hottopicsinneonatology.nemours.org/registration.html

Don’t miss the live session continuing this conversation: Pressure, Flow, and the Grey

Areas In Between. Presented by Fisher & Paykel Healthcare. Monday, December 7 at 11:45 AM. Full agenda: https://hottopicsinneonatology.nemours.org/agenda.html

Link to episode on youtube: https://youtu.be/gKtXcTcBgIw

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The articles covered on today’s episode of the podcast can be found here 👇

HIPSTER trial. Roberts CT, Owen LS, Manley BJ, et al. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. N Engl J Med. 2016. https://pubmed.ncbi.nlm.nih.gov/27653564/

HUNTER trial. Manley BJ, Arnolda GRB, Wright IMR, et al. Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries. N Engl J Med. 2019. https://pubmed.ncbi.nlm.nih.gov/31116919/

ÉCLAT trial. Kidman AM, Manley BJ, Boland RA, et al. Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (ÉCLAT): a multicentre, randomised, superiority trial. Lancet Child Adolesc Health. 2023.https://pubmed.ncbi.nlm.nih.gov/38240784/

PHILODENDROOM pilot trial. Cavigioli F, et al. Initial CPAP of 5 versus 8 cmH2O during delivery room stabilisation of very preterm infants: the PHILODENDROOM pilot randomised trial. Eur J Pediatr. 2026.https://pubmed.ncbi.nlm.nih.gov/42608615/

NIPPV trial. Kirpalani H, Millar D, Lemyre B, et al. A Trial Comparing Noninvasive Ventilation Strategies in Preterm Infants. N Engl J Med. 2013. https://pubmed.ncbi.nlm.nih.gov/23944299/

Extended CPAP trial. Lam R, Schilling D, Scottoline B, et al. (McEvoy CT, senior author). The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial. J Pediatr. 2020. https://pubmed.ncbi.nlm.nih.gov/31519441/

Cochrane network meta-analysis. Razak A, Shah PS, Kadam M, Borhan S, Mukerji A. Postextubation use of non-invasive respiratory support in preterm infants: a network meta-analysis. Cochrane Database Syst Rev. 2025. https://pubmed.ncbi.nlm.nih.gov/40643582/

Cochrane review. Lemyre B, Deguise MO, Benson P, Kirpalani H, De Paoli AG, Davis PG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2023. https://pubmed.ncbi.nlm.nih.gov/37497794/

SUPPORT trial. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Early CPAP versus Surfactant in Extremely Preterm Infants. N Engl J Med. 2010. https://pubmed.ncbi.nlm.nih.gov/20472939/

COIN trial. Morley CJ, Davis PG, Doyle LW, et al. Nasal CPAP or Intubation at Birth for Very Preterm Infants. N Engl J Med. 2008. https://pubmed.ncbi.nlm.nih.gov/18272893/

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The transcript of today's episode can be found below 👇

Ben Courchia, MD (00:00.654)Hello everybody, welcome back to The Incubator Podcast. We’re back today for our special series on non-invasive ventilation, and we have the pleasure of welcoming back into The Incubator studio Dr. Brett Manley. Can I call you Professor Brett Manley yet, or no?

Brett Manley (00:14.453)How about just Brett, Ben? That’ll be great.

Ben Courchia, MD (00:17.475)That’s great.

Brett Manley (00:18.015)But yeah, you can call me whatever you like.

Ben Courchia, MD (00:20.394)Okay. I like the humility. So Brett, thank you so much for coming back to the podcast. People are familiar with your work, and your bio is going to be available on the site. You are joining us today from Australia, and we’re very happy to talk to you a little bit about non-invasive ventilation, to talk a little bit about how we use non-invasive ventilation at which stages of the hospitalization, and see what the evidence says, and maybe shine a light on some of the ways in which practice has sometimes deviated from what the evidence shows. I think this will be a very interesting conversation. I guess my first question for you is, if you have to think of non-invasive ventilation, what kind of modes are you thinking of, and what kind of delivery apparatus are you thinking of? I think we’ve addressed this on the podcast before, but the interface obviously makes a huge difference, because it’s very difficult to claim that we are delivering CPAP through a very small nasal cannula with lots of leakage. So I’m just curious, in your mind, in the mind of Brett Manley, how do you think of non-invasive? What are the different big-ticket items that appear?

Brett Manley (01:39.657)This is part of the problem, isn’t it? And not only with non-invasive ventilation, but mechanical ventilation and other things, is the number of devices and modalities that are available, with people doing lots of different things. We used the word “messy” just before we came on, didn’t we? It makes it quite messy to sort through all of this. I mean, you’ve got your CPAP; that’s been the mainstay. But we all know that CPAP comes in various forms. You’ve got your ventilator CPAP, your Infant Flow drivers, which I’ve never really used, and bubble CPAP, trusty old bubble CPAP.

There are some limitations to each of those types of CPAP. They do some things better than others, and each unit and many clinicians will have their favorite. You’ve got the add-ons to CPAP. You’ve got your nasal intermittent positive pressure ventilation, or nasal IMV, whatever you call it in your part of the world, and that can be synchronized or unsynchronized, non-synchronized with the baby’s breathing, and that might be critically important. And therein lies another problem with the literature and trying to work our way through this. You’ve got nasal high flow, something that I’ve studied quite a bit at the start of my career, which has become kind of ubiquitous with respiratory support for preterm babies and is being used a lot around the world, maybe not in the optimal fashion, and we can discuss that. And then you’ve got the newer modes. You’ve got your NIV-NAVA, nasal high-frequency ventilation, again, things that I haven’t personally used very much, but are becoming more common in Australia and more common around the world.

Ben Courchia, MD (03:07.51)Mm-hmm. Absolutely. As you said, every mode has its own specifications. I’ve heard from Guilherme Sant’Anna in Canada that bubble CPAP, for example, does provide a little bit of non-invasive high frequency, with these bubbles taking place at such a rapid pace. I’m just thinking in terms of clarification: when we talk about high flow nasal cannula, what does that mean specifically? I’ve heard, in passing, and I’m not going to say from whom, people say, “This baby is on one liter of high flow nasal cannula.” Is there a certain point where nasal cannula becomes high flow? And is there a point at which, no, you’re on low flow, irrespective of whether you have it connected to various devices?

Brett Manley (03:55.229)Yeah, well, there are a few things in there, aren’t there? Firstly, I think for nasal high flow to be different from just nasal cannula oxygen off the wall, there are some important features of nasal high flow. It should be heated and humidified gas. That’s the first thing, just like other modes of non-invasive support. And then the actual flow going to the baby should be doing something. And I’m not sure we know exactly what the gas flow should be to be doing something, but in my practice, and in our practice, it’s certainly changed over time. We now rarely would go below four liters per minute with nasal high flow. So that’s been a cutoff point that has evolved. It used to be more like two liters per minute; now it’s four liters per minute. And below that, you’re really not generating any distending pressure, and you start to get into problems as the babies get bigger with not even delivering the oxygen, the fraction of inspired oxygen, that you think you should be. So I think four is a good lower limit for a definition and a clinical use of high flow. It also helps to avoid a major problem with high flow that is ongoing, which is this feeling that you should wean it eight, seven, six, five, four, three, two, one. Some centers even wean it by half a liter per minute; some centers even wean it by less than that. And I think those tiny decrements and increments just don’t make any sense. So in our centers it’s eight, seven, six, five, four, and the baby’s off. And if they need oxygen, they’re on low flow, or they’re on nothing. And many of these babies are in air on high flow, which is another ongoing issue. I’m giving a talk later today in Brisbane, Australia, at a tiny babies seminar about what BPD is. What should BPD be defined as? And I know that’s not the topic for today. But clearly, if you’re going to say that nasal high flow is respiratory support, especially if you’re going to say that one liter per minute or two liters per minute in air is respiratory support, and those babies are on that at 36 weeks, you’re giving them a diagnosis of BPD when in fact they may have very little lung disease and no oxygen requirement. So we create problems for ourselves in the way that we use therapies and the way we define things like BPD. So what I would recommend for centers is that my usual maximum for high flow is eight, although I’m starting to see it be turned up higher than that, just like every other type of non-invasive support. And my usual minimum for high flow would be four liters per minute, at which point I’d be taking the baby off.

Ben Courchia, MD (06:27.211)I know people are going to ask that question in the car as they’re listening. This high limit of high flow of eight, do you have a specific weight cutoff that you apply this to? Is this for a convalescing 36-weeker, or do you feel comfortable with a 28-weeker who’s extubated and doing quite well being on these types of flows?

Brett Manley (06:45.598)To be honest, that number really comes from the manufacturers of the high flow devices that have set that as a maximum. It’s partly what was set at the time, which was a little bit made up, but also the devices simply can’t deliver gas flows effectively higher than that with the really tiny cannula. Now that’s changing. I know the Fisher & Paykel devices, for example, I think they now go up to nine, even in the smallest prongs, so you can actually deliver that gas flow rate without there being pressure within the system that gets blown off, so it becomes irrelevant. But that’s really where the numbers come from. Also, those are the numbers that have been tested in clinical trials. So in our clinical trials of nasal high flow, the highest we’ve gone in any of those trials is eight liters per minute before changing to a different modality. That doesn’t mean that in the future we won’t want to use higher gas flows. Maybe we will.

Ben Courchia, MD (07:32.271)Fair enough. Maybe we will. For the purpose of this conversation, I think we should just lay to rest the discussion about interface. I think we can agree that if we’re going to talk about CPAP, we mean that pressure is delivered through an interface that doesn’t allow for any leakage, or at least very negligible leakage. There may always be a little bit. But the idea being that when you decide to deliver pressure through CPAP, through NIMV or NIPPV, it is delivered to an interface that is designed to do that. And when we’re going to talk about high flow nasal cannula, we talk about interfaces that have a lot more leakage around them. Do you think that’s okay for us to do, or what are your thoughts on... okay.

Brett Manley (08:17.044)100%, 100%. And there’s, of course, nuance around that. People might say, well, you can deliver pressure with high flow, and you can. That’s been measured in many studies. The smaller the baby, the higher the flow, the larger the cannula, the more it occludes the nares. Of course, you can generate significant distending pressure in the lung. But I totally agree with you. CPAP means a minimization of leak, aiming to generate a continuous pressure. High flow is the smaller nasal cannula, and really, by definition, there’s a leak.

Ben Courchia, MD (08:46.755)Very good. So then I think one of the guiding principles that we’ve all been trained with is the idea that, specifically for preterm infants in general, and obviously we can differentiate the types of preterm infants, but irrespective of that, we’ve been trained that minimizing exposure to invasive mechanical ventilation is good, and it leads to better outcomes down the road. And so the real question has been, then, what is the best way to support these infants after birth, if they allow us to do that, when it comes to maintaining their respiratory needs on non-invasive? And I think that for the past 10 to 15 years, there have been a few strong trials that have been conducted looking at that. Looking at early CPAP has been one of the most cited papers published in the New England Journal. But that has shifted as well in terms of, what about initiating high flow nasal cannula right off the bat? So in your mind, can you tell us what the evidence shows, and whether we can think of preemies as a whole, or do we have to differentiate preemies? I know that Roger Soll was on the podcast not too long ago and was mentioning that he does think a bit differently for these very, very tiny infants and their respiratory needs compared to maybe more mature infants, like, let’s say, a 30-weeker. So based on the data that you’ve reviewed, and you’ve been involved in a lot of these trials, how do you teach this to others?

Brett Manley (10:28.972)Yeah, and as we were speaking about before we came on as well, everybody has different equipment and different culture and different likes and dislikes. And so I’m well aware that practice varies dramatically around the world. Just as an example, many units would start very preterm babies or extremely preterm babies who don’t immediately need to be intubated on CPAP. The pressure that would be used in that situation varies dramatically around the world. There would be some centers that would not routinely go above five centimeters of water. There would be others that would use seven or eight or even higher pressures right off the bat in these babies, either before or after they’ve received surfactant. There are some centers... Go ahead.

Ben Courchia, MD (11:09.123)Yeah, we reviewed a very recent study that was published, the PHILODENDROOM trial, looking exactly at that, about whether there is feasibility in starting much higher CPAP levels in the stabilization of very preterm infants. So it’s definitely a topic of conversation.

Brett Manley (11:30.45)Yeah, and I think that largely may depend on whether the baby’s had surfactant or not. I certainly personally get worried about pneumothorax and other problems when the pressures go really high in a baby who’s de facto surfactant deplete, but everything changes once the surfactant’s in. It’s the same argument with post-extubation support. But back to the primary support question. There are some centers... I’ve been visiting some centers in Australia recently that, particularly for their small babies, will be starting NIV-NAVA right from the start, right from straight after the delivery room. The babies are on NIV-NAVA, synchronized NIPPV, the surfactant’s in, and the baby’s on NIV-NAVA. I think the most common scenario is CPAP. We’ve looked at using nasal high flow as a primary mode of respiratory support in preterm babies. We’ve done a couple of trials there, albeit they have not included extremely preterm babies. So Calum Roberts led the HIPSTER trial, which looked at high flow versus CPAP for that group that are 28 weeks up to 36 weeks. So preterm babies, but not extremely preterm babies. And at the same time, we actually did a trial in non-tertiary units, in non-NICU hospitals, who don’t look after those very preterm infants, only more mature, late preterm and term babies. And that was the HUNTER trial, yeah.

Ben Courchia, MD (12:45.2)That was the HUNTER trial, right?

Brett Manley (12:48.282)And both those trials came out around the same time, and they both showed strikingly similar results, which basically is that they were both non-inferiority trials aiming to show whether high flow was as good as CPAP, and it wasn’t. So CPAP outperformed high flow in terms of treatment failure, which was a trial definition about a certain amount of oxygen and blood gases, apnea, et cetera.

They did also, however, both show that you could start using high flow and then switch the baby across to CPAP without any adverse outcome. So that treatment protocol of starting with high flow, seeing what happens, and changing the baby to CPAP if they hit certain thresholds, that seemed to be quite a reasonable thing to do. Again, these are not extremely preterm babies. But I think what’s really happened since the publication of those two trials is people have said, yep, we sort of thought that babies with RDS with an oxygen requirement who are sicker, they need CPAP, they need that continuous distending pressure. And that’s certainly what’s happening in my practice. I’ve moved away from using high flow as a primary mode of support in all but the most well babies with a bit of respiratory distress or TTN, and they’re all getting CPAP. And then, of course, the question is how high do you turn it? And it varies greatly. In my own practice, I’d be using CPAP of something like seven or eight centimeters of water, getting some surfactant in if we needed to, and then determining whether the baby needed intubating after that. And I think that’s probably about where a lot of centers have ended up with CPAP. I can’t talk much about other modalities, and there’ll be people out there using nasal high frequency or NIV-NAVA, as I say, with great success. And these things probably need to be tested in larger trials before we can be sure.

Ben Courchia, MD (14:36.526)Yeah, and I think that both the HIPSTER and the HUNTER trial started with CPAP between six and eight, I think, at birth, comparing to high flow of six to eight liters as well. And I agree with you. I think that high-frequency nasal ventilation is still... I have yet to be at a center where this is available. I think there are certain centers that use it. And NIV-NAVA at birth as well is something that will be very dependent, in my opinion, on the type of patient that you’re admitting.

There are also, interestingly enough, some very clear contraindications to the use of NAVA. And so I think that you may need to know a little bit more sometimes about your patient before you initiate that, whether there’s any brain issue or congenital diaphragmatic hernia, things like that that obviously need to be addressed.

Brett Manley (15:26.45)Yeah, I don’t think we should be suggesting anyone goes out and just grabs a new mode of non-invasive support and starts using it. It’s a cultural shift. It requires buy-in from your nursing staff, with all of these things, and a lot of practice to get it right.

Ben Courchia, MD (15:30.885)Yeah.

Ben Courchia, MD (15:34.946)Absolutely.

Ben Courchia, MD (15:41.337)And so you mentioned something earlier, in the point you were making about these trials, showing that if you use high flow nasal cannula, there is enough evidence to say that it’s okay to initiate high flow nasal cannula with the possibility of a transition to CPAP. And you mentioned that this would be dependent on whether the baby develops certain types of symptoms. And understanding that the respiratory course of these infants after birth is quite well described, and we know that they tend to do quite well in the first few hours after birth and that slowly, over time, that inflammation kicks in, what are some of the things that you’re looking for, beyond the natural course of their respiratory disease, that can tell you that they are no longer doing so well on high flow nasal cannula and that this might need escalation of support?

Brett Manley (16:27.73)Yeah, well, firstly, you need to decide what your own maximum gas flow for your high flow is. For me, in the first days of life, that’s eight liters per minute. So a baby on eight liters per minute who has an oxygen requirement greater than X, and I think for me it’s probably 40 percent, that’s what we used in the trials; who’s developing apnea or hypopnea that’s increasing in severity or frequency; or a worrying blood gas. Those are the top three.

We tried to keep things fairly objective in the trials, but I know work of breathing, which, that expression’s been banned in some units because it’s very subjective. But work of breathing is something that people really worry about. And so tachypnea, significant subcostal recession, et cetera, would be enough for many units to change from high flow to another mode.

Ben Courchia, MD (17:05.52)

Ben Courchia, MD (17:18.98)Daphna and I were having this discussion, not an argument, about work of breathing. And she was making the point that when she trained, she was told that you should not have any work of breathing, that breathing should not be something you work at. You breathe. And I was trained in a place where your work of breathing could be normal or increased. And so we were trying to discuss that in terms of our documentation and what we actually call our assessment. So you’re absolutely right that the semantics of

Brett Manley (17:33.373)Mm-hmm.

Ben Courchia, MD (17:46.171)breathing definitely exist and are culture-based. And so in this conversation, obviously, the question really remains, why not NIMV? Where is NIMV in this conversation? Where is, let’s say, a standard non-synchronized form of non-invasive intermittent mechanical ventilation? Also understanding, as we’re going to talk about post-extubation afterwards, that we know in post-extubation there’s lots of data that show that NIMV does really, really well. So what about after birth? Isn’t that maybe a better solution?

Brett Manley (18:27.474)Yeah, well, this is definitely an area of controversy that we need to sort out as a community. There is both unsynchronized, or non-synchronized, NIPPV or NIMV, where the ventilator, or the machine that you’re using to generate that, tries to give an inflation that’s not synchronized with the baby’s breathing.

There’s synchronized, which in the Cochrane reviews and the systematic reviews seems to come out top, particularly as post-extubation support. So that’s where those inflations or breaths are synchronized with the baby’s attempts to breathe. And then throw into the mix higher CPAP, because a lot of the controversy here around NIMV and NIPPV is whether the beneficial effect, if there is one, is from those attempted inflations, whether it’s to stimulate breathing or to actually inflate the lungs, or whether we’re actually just talking about a higher mean airway pressure. So it’s just a cheat, where you have your CPAP and then you put some extra inflations on top and the mean airway pressure goes up. And I believe that that is where we need to sort this out. We conducted a smallish RCT called the ÉCLAT trial a few years back, led by Anna Kidman, and in that trial we extubated extremely preterm babies to either what we were calling standard CPAP of seven centimeters of water, which might be higher than some centers, or a higher CPAP of 10. And in the higher group, it could go as high as 11 centimeters of water. And we found that higher CPAP to be superior at avoiding extubation failure to the standard CPAP pressures. So prior to that, there’d been only a couple of other very small RCTs, and there remain only a few small RCTs on that entire topic of higher CPAP pressures after extubation in extremely preterm babies. So those sorts of mean airway pressures we were extubating babies to are very similar, if you’ll allow me to call it mean airway pressure when it’s CPAP, very similar to the mean airway pressures that are used or prescribed with NIPPV or NIMV. So is it simply that babies might need more pressure,

Brett Manley (20:38.074)or is there something actually better about the way that NIPPV works? And I think we need to sort through that, because at this stage I’m not convinced that unsynchronized, non-synchronized NIPPV is in itself a particularly useful therapy. And we could argue... I think we could have an hour on that, and maybe that’s a topic that will come up in our conversations later in the year at Hot Topics. Because that very question is a really important one that sees some units using non-synchronized, some using synchronized, and some not using it at all and just turning the CPAP up higher.

Ben Courchia, MD (21:11.845)Yeah, I think this is interesting because it highlights a bit of an area of darkness, where really we don’t know what the effect or the benefits of NIPPV are. And you mentioned the recent publication of the ÉCLAT trial in The Lancet; I believe it was in 2023. We’re going to link, by the way, all the papers that we mention in this particular episode in the show notes so that people can access the data that we are reviewing.

Brett Manley (21:40.646)And I’m aware there are people out there planning such trials. And the key here is that I think if you want to compare modalities, such as NIPPV to CPAP, plain CPAP, then matching them in mean airway pressures, at least at the start, is an important feature of such a trial.

Ben Courchia, MD (21:57.21)Yeah. That’s a very good point. So we’re discussing, obviously, the non-invasive intervention as primary modes of ventilation, and we’ve been talking about this for some time now. I feel like there are two other categories in which non-invasive really becomes a topic of controversy. The first one is, as we just alluded to, the post-extubation phase. I feel like this is where the different categories of non-invasive ventilation that you mentioned at the onset of this episode are really key. And I remember this particular graph, I forget what it is called, that was published in the Cochrane Review of the different modes of ventilation that are available after extubation. And it basically showed them in different bubbles, and they were connected by yellow lines whose thickness was basically related to the number of patients that were actually studied comparing different modes, and the variability of the thickness of these lines. You had some that were quite thick when you were comparing NIMV to CPAP. And when NIV-NAVA was entering the fold, there was like a hair. So it feels like we don’t have consistency of data when it comes to all the modes being compared equally to one another. And I think that also creates confusion, because we might hear that a mode is doing better after extubation, but in the specific studies, what was that compared to? And that’s all you really can draw conclusions on. So is there at this stage, in your opinion, based on the data, a hierarchy of modes that, if you’re going to extubate a baby, are better than others?

Brett Manley (23:41.565)I think you’re probably referring to one of the network meta-analyses, and gosh, it is messy. It’s really hard to get your head around and to work out A versus B versus C versus D, and then get A versus D out of that. Look, I think the evidence from the systematic reviews and other trials, and I think also of Haresh Kirpalani’s NIPPV trial, I think it’s pointing us towards synchronized NIPPV, of the common modes, as

Ben Courchia, MD (23:45.061)That’s right.

Ben Courchia, MD (23:54.769)That’s right.

Brett Manley (24:11.54)possibly a superior mode. But again, I think that before we can determine that, that needs to be compared against higher CPAP pressures. I think they’re the most promising modalities for keeping extremely preterm babies off mechanical ventilation, especially as post-extubation support, as many of these babies are receiving.

So that would be the comparison that I would be most interested in, and they would be the modes of ventilation that I would choose to use. Now, again, some centers have NIV-NAVA, which is a specific way of synchronizing NIPPV, and swear by it, and have anecdotally great results. And I’ve seen some of these babies doing great on NIV-NAVA, but haven’t used it myself. And similarly, nasal high-frequency ventilation is being used in Europe, and the centers that are using it well and consistently are claiming good results. So they would be the modalities I would be most interested in, and certainly in my hospital, that doesn’t have some of those newer, fancier modes, I’m always thinking about higher CPAP and/or synchronized NIPPV if it’s available.

Ben Courchia, MD (25:22.834)So you’ve talked about synchronized NIPPV quite a few times already. And I’ve worked in a lot of units where that is not even an option. So I’m just wondering, for the people who don’t have synchronized NIPPV in their unit, is there something you can describe as to how the babies are actually synchronized? Because obviously in NIV-NAVA, we understand that the NAVA catheter, which is the feature of this particular mode, is how babies are synchronized. But for a baby that has a mask or Hudson prongs or whatever that may be, how does the vent synchronize with the patient? Can you just tell us briefly how that works? Because we know that with the intubated patients you have these flow sensors. Does that work similarly, for people who are not familiar with the tech?

Brett Manley (26:05.126)And to be clear, Ben, my center and my previous center also don’t have synchronized NIPPV. So I’ve seen it used, but haven’t used it a lot myself in my own clinical practice. So there’ll be others out there that will be more expert in this. But there are multiple ways of synchronizing the breathing. And part of the issue is having the equipment, having the ventilator, having the machine that actually does that. And when we talk about not having that mode, it’s because we don’t have the machine that can deliver that mode or has that ability. And I know that ventilator manufacturers are now trying to make sure that they have a way of doing that, but at the moment there’s only a few that do. So you need to have the ventilator machine that can do it, and then you need whatever the mode of synchronization is with that machine. There are Graseby capsules, capsules that detect the movement of the abdomen and try and synchronize the breathing that way. There are flow sensors that can be inserted into the circuit. And there are, in the case of NIV-NAVA, as you said, that’s detecting the diaphragmatic electrical activity through a tube down into the stomach. So multiple ways of doing it. I think people who use NIV-NAVA, and the manufacturers, would say that they have the best way of synchronizing. But again, not having used it myself in clinical practice, I think it’s hard for me to comment on which one might be best. But you can’t just go out and do it. You need the equipment.

Ben Courchia, MD (27:28.464)Absolutely. And I think that’s helpful. I think that’s helpful even for people to understand as well that there’s synchronization and there’s synchronization. There’s synchronization on invasive ventilation, which obviously can be done quite well. And I think that when you get into the non-invasive modes, there’s a lot more error that can enter the fold, and then you get into the ranking, where people say this is the best way to synchronize, this is not the best way, and so on. In terms of...

we started alluding to this earlier on in the episode, but let’s say that we have babies that have been extubated and they’re convalescing. And I feel like for many clinicians, this period of non-invasive ventilation can feel like an eternity. And it’s like, my God, these babies are on non-invasive for the longest time. And I think it could be frustrating, and it then leads to questions of, are we on the right mode? Do we need more pressure? Why can’t we wean this patient? There’s lots of data discussing timing of liberation from respiratory support, saying that these are kind of the time frames, and these are quite long. But what is an approach that makes sense based on the types of babies and the evolution of their needs on non-invasive after they’re extubated? Meaning we’ve passed that seven-day mark. We know that they’ve succeeded. They’re not going to get re-intubated, but then they stay on non-invasive support for a very long time. And not in the Cindy McEvoy way, meaning they need it. Like, you’re just having difficulties. What is your approach to these infants specifically?

Brett Manley (29:08.53)Yeah, it’s another really tricky area that we need to try and get some more answers in. And this is really being brought home by our patient population changing over the last decade. And I’m going to present some data at the conference I’m at today about how many of our tiny babies spend more than a hundred days on respiratory support, which is just crazy when you think about it. And I think the trick is knowing whether they need it or it’s just us doing it.

And I don’t think we have all of those answers right now. And there are a lot of questions that go into what a baby should be on. If they need oxygen, what’s the best way to provide it? If they need pressure, what’s the best way to provide it? And then throw in the need for good neurodevelopmental care of these babies as they’re developing and trying to, for example, establish suck feeds. And that’s why I find Cindy’s trial so interesting, and, when thinking about replicating Cindy’s trial, how I would take into account the need for babies to suck feed if we were extending their CPAP on purpose for a week or two or longer, as they reach that postmenstrual age where their brain’s saying, hey, I want to actually start to suck my feeds now. So it’s complicated. The evidence out there is not great to tell us what to do. I think,

Ben Courchia, MD (30:19.143)Mm-hmm.

Brett Manley (30:31.494)if we look at what’s actually happening in practice, there are babies getting CPAP or NIPPV for a period of time as they evolve with their chronic lung disease or convalesce with their chronic lung disease. I think it’s really common to see those babies then change to nasal high flow at some point. And that point is different for every person. For me, an extremely preterm baby who’s on respiratory support, who’s a few weeks or months old, once they’re getting down to a CPAP of around five or six, they’re looking nice and stable, perhaps they’re in 30 percent oxygen or less, is about the time where I would routinely consider switching across to high flow. I think some would argue, why bother? You’re just changing a mode of respiratory support. But for me, I know that some of this is not very scientific, but you’ve only got to see the look on the parents’ face, the nurse’s face, your own face when the baby is off CPAP, looks way more comfortable, and just seems to be enjoying life a little bit more on the nasal high flow. That’s a good enough reason. And then it’s how fast you wean the high flow part of that. And again, everybody does it differently. I mentioned right at the start, eight, seven, six, five, four, and then off for me, and then on to low flow nasal cannula. But we do have to remember that high flow has come in over the last two decades, but before that, people would just go CPAP and then off, or CPAP to low flow nasal oxygen.

So we’ve added in another modality, and that has created... it’s good for the babies, but it has created more complexity, because there’s a tendency to leave them on the high flow for a long time, and then, depending on your definitions of BPD, suddenly you’ve got a whole other population getting diagnosed with BPD at 36 weeks because they’re on a small amount of high flow. So it’s complicated. Sorry, Ben, go ahead.

Ben Courchia, MD (32:18.269)Yeah, and

No, and so that means that basically you don’t necessarily commit babies to high flow no matter what. You can take them off CPAP and straight to room air in your practice. Is that something that you’ve done in the past as well?

Brett Manley (32:34.292)I think if I’m honest with myself, I would say that for the small babies, let’s say under a kilo, I would rarely take them off respiratory support until they were bigger and stronger and well over a kilogram. So I would commonly give them a tail of nasal high flow, if you like, for days or weeks, especially if their oxygen requirement is low. I mean, one of the things we thought about with high flow when it first became popular was,

Ben Courchia, MD (32:49.01)Yeah.

Brett Manley (32:59.272)would it actually be better to be on high flow than low flow oxygen? For example, if you could be on high flow in air, would that be better than being on low flow nasal cannula with an effective FiO2 of 25 or 30 percent? I don’t think that’s been borne out in the cohorts that we’ve looked at to see whether that reduces ROP or anything else. So I think high flow has become a comfortable, commonly used, easy-to-use modality in this situation we’re talking about.

The question is when we should be stopping it and how we should be limiting a diagnosis of BPD, if we think that’s important. And one thing leads to another, doesn’t it? And as time goes by, the definition of BPD at 36 weeks is becoming not very useful anyway. So maybe it doesn’t matter that a baby’s on nasal high flow at 36 weeks, but when you think about hospital resources, you think about diagnoses, funding, and all the rest, everything we do has an impact. Now, there have been some small trials of how and when you should wean babies off CPAP, either onto high flow or onto nothing or onto low flow oxygen. They all show fairly mixed results. And part of the problem there is that the protocols in the trial really dictate what’s happened. It’s not baby-driven; it’s more about you give this for this long and then you wean it in this way. And of course, if you wean by half a liter every day versus one liter every day, of course that changes your time on respiratory support. So it’s very complex. And this is something that I’m certainly interested in looking at, how best to wean babies from CPAP support through that convalescent phase. So I don’t have all the answers there. I would commonly go from CPAP to high flow in extremely preterm babies as they grow, as a comfortable modality, and then try and pick the moment where I think that the pressure’s less important and the oxygen is more important to get them on to low flow nasal cannula.

Ben Courchia, MD (34:54.5)Very, very good. You mentioned something in your response about having an assessment of a baby needing pressure versus oxygen. And I think there’s a stigma about us using too much oxygen, which often leads us to not give enough oxygen to the baby who needs oxygen more than they need pressure. How do you differentiate between the two in your practice?

Brett Manley (35:16.732)The two go together, and it’s difficult to pull them apart. Those of us working in tertiary neonatal units looking after the tiny babies, we’re seeing our patients change before our eyes. We’re getting used to babies needing more oxygen even in the first week of life, the week after birth. We’re seeing it’s quite routine for tiny babies to be in 30, 40, 50 percent oxygen by seven days after birth.

And we need to get used to that and really think about how we’re managing that. And it’s the same with non-invasive support. We’re now seeing more and more babies, even approaching term, that are in way more oxygen than we have seen before, at least in my part of the world. And so we’re having to get used to what that looks like, and be a little bit more conservative in the way that we... well, I’m not sure conservative is the right word. We have to get used to whether we’re comfortable weaning their respiratory support knowing that they need a lot of oxygen. Whereas in the past, we would have been maybe turning up their respiratory support and been unhappy or worried about the amount of oxygen they were receiving. So that’s changing as well. For me, it’s just a matter of time. It’s a gradual wean of the... I use mainly CPAP, a gradual wean of the CPAP, to see whether that really affects their oxygen requirement or not. I do sneakily have a little bit of a look at their work of breathing, in inverted commas, and their respiratory rate. I see how the baby’s growing and feeding. If all of those things are going well and the baby’s in the same amount of oxygen even when I wean the CPAP, I’m starting to think maybe it’s not so much about the pressure. I keep going down on the CPAP and then see whether I can get the baby on to high flow successfully. And the numbers I change over from, like I said earlier, CPAP of maybe five or six centimeters of water, but this is just personal opinion, this is not proven, and then switch over to a high flow of maybe seven or eight liters per minute and then wean the high flow down as well. And then the babies will tell you what’s working for them. And if you’re very quickly able to wean down every day and suddenly the baby’s down on a high flow of four in not much oxygen, I think about whether they’re big enough to switch over to low flow nasal cannula.

Ben Courchia, MD (37:23.474)Yeah. Very, very interesting. We’re almost getting to the end of our time here. And we’ll obviously keep that conversation going at Hot Topics in Neonatology. If you want to join us for that, please make sure you go and register for that conference, taking place in the first week of December in Washington. The question that I have, I guess, is, we’ve talked a lot about some of the tools that we have. We’ve talked about the data that we currently have, and we’ve talked about the data that we don’t have. And so I’m curious, in your mind right now, of all the things that need to be tested, what is, in your opinion, the highest priority? You’ve already mentioned doing more trials of interfaces and modes of support that are equal in mean airway pressure.

But what is the next immediate question that we need to have an answer to in order to affect practice in a significant way, you think?

Brett Manley (38:27.262)Well, firstly, I’m very interested in Cindy’s and her team’s ongoing work with prolonging CPAP for lung growth to improve longer-term outcomes. And I think there’s more work to be done around that. But like I say, when I think about that, there are lots of other things that you need to consider other than just putting the baby on CPAP for longer, and I’m sure we’ll talk about this at Hot Topics. For me, I think sorting out the best mode of non-invasive support for extremely preterm babies, particularly coming off the ventilator, is an important topic. I think that comparison between synchronized NIPPV and higher CPAP needs to happen in a good way. And like I say, I know that there are people out there thinking of doing it. There may even be some trials that have already started comparing higher CPAP, and what we’ve used in the past, to synchronized NIPPV. I think that would really help to reduce some of the murkiness here, because at the moment I think people really aren’t sure which is the best mode to use, in particular in those extremely preterm babies. And I think the second topic is what we’ve just been talking about. What are some of the protocols or ways that we can be weaning babies from respiratory support for that really prolonged period, from more than a few weeks of age until they’re up to term, for our extremely preterm babies and now particularly our tiniest babies? Is there a good way to do that that maximizes lung growth and function whilst also taking into account neurodevelopmental care and comfort?

Ben Courchia, MD (39:59.382)So one of the big questions, maybe my last question, obviously, is about these infants. I think that the question of tracheostomy, in babies who have been convalescing, who can’t get off significant non-invasive support, obviously the question is always asked: do they need a trach? Do we just wait longer? And it’s a big decision for the families, for the babies, and for us as a clinical team, because effectively it is not an equal transition. I think that going to a tracheostomy moves you back to an invasive mode of ventilation. I’m just curious... speaking to a lot of people on the podcast, I think there was discussion several years ago about the fact that an early tracheostomy might lead to better outcomes down the road because of all the neurodevelopmental things you could do. And more and more we’re hearing people saying, well, we’ll wait as long as it takes if we can avoid the tracheostomy, which again means you’re going to have to manage these infants on non-invasive or other modes of ventilation for longer periods of time. I’m curious as to where you stand on that tail end of the course, where ultimately you have to make a decision as to where the care goes next.

Brett Manley (41:11.58)Well, like a lot of people listening, I’m very much learning from others in this area, because in Australia and in my part of the world, tracheostomy has been an extremely rare outcome for our babies in the past. But now we’re starting to see this needing to happen more and more, as the babies with really severe BPD are being referred for ongoing respiratory management at term or beyond.

And that includes, do they need home ventilation, home respiratory support, and tracheostomy? So I’m not the expert here, but I listen to some of the world experts from some of the centers of excellence, particularly in the States, talk about that exact conundrum that you’ve just described, early versus late tracheostomy. The trialist in me says that’s a great opportunity to compare two groups where we’re in equipoise.

It’s complicated, because I understand how complicated these babies are at the point you’re making these decisions, but I think that needs to be studied. A very difficult trial to do, but perhaps someone out there who looks after this population of babies every day could take this on.

Ben Courchia, MD (42:16.511)The third approach, which is being floated out there, is obviously, why don’t we send these children home on non-invasive ventilation? Do you have any... I don’t think this is a very practical or proven method yet, but I’m just curious about the trialist in you. Do you think this is feasible? Do you think that this has a future?

Brett Manley (42:40.328)Well, we’re starting to move away from science and into government policy and finances here, because obviously to provide that service you need to have that service. Incredibly expensive, labor intensive, scary for families. You need to have resources. I know some countries have step-down hospitals or hospices where babies can be “discharged” to, in inverted commas, and then spend a lot of time on non-invasive support. Others can provide that support at home.

Again, in my part of the world... Yeah.

Ben Courchia, MD (43:09.885)Is it safe? Is it safe, do you think, though?

And we... I almost should have a little jingle that says we’re now going away from any sort of expert opinion and more into just a hunch. But I’m just curious, when you’re looking at this, this is so premature. This is just cracking the surface as even a question. And again, the tech might change the way we answer this question today. We might end up with devices that are so much better that it’s much more feasible.

I don’t particularly think it’s safe based on... even in high-resource environments, it seems like it might be a recipe for disaster. But I’m just curious if you think differently, or if you think, no, this may have a future and it’s worth looking into.

Brett Manley (43:59.615)Look, I think it’s practical that children could go home on respiratory support, and some people in the audience listening will already be doing this. These are, by definition, the sickest of the sickest babies. I’m presuming we’re mainly talking about extremely preterm infants that are now way past term, maybe months and months past term, and they’re going home on respiratory support. We know how hard it is to manage that in hospitals. So asking families to do that,

Ben Courchia, MD (44:08.246)Mm-hmm.

Brett Manley (44:28.07)albeit I’m sure with a lot of support, that must be intimidating. I guess we need to ask the families what they want, and I can think of some people that would be great to do that. Because

Ben Courchia, MD (44:38.038)I wouldn’t be surprised if some families might say, sure, I’ll do it. We’ve both encountered families that are so motivated, so dedicated, and for them, maybe staving off a tracheostomy is very, very, very important. And getting out of the hospital. And I’ve seen parents who, based on whatever background they have, know a lot about the ventilator by the time they leave. They know.

Brett Manley (44:54.93)And getting out of the hospital and getting into their own home environment. Yeah.

Brett Manley (45:07.09)Well, this will be a great conversation topic for Hot Topics, and I’m sure at Hot Topics there’ll be plenty of people that have done this, and they’ll have their own experiences, and they’ll be good and bad. The parallel would be home oxygen. There are some families that, as they’re getting to 36 weeks, they’re like, yeah, get me out of here on the oxygen. I want to get out. And there are others that would rather stay in hospital another two months and go home without oxygen. And I understand both of those standpoints.

Ben Courchia, MD (45:07.605)Well

Ben Courchia, MD (45:12.372)Yeah.

Ben Courchia, MD (45:23.008)Get me out of here. Mm-hmm.

Ben Courchia, MD (45:28.436)Yeah. Yeah.

Ben Courchia, MD (45:32.471)Yeah, it will be very interesting to see how we integrate what the data shows, what the technology allows, and what families consider priorities into maybe a future trial. It’s definitely very interesting. And it extends, obviously... to me, the reason I wanted to conclude with this is because it shows how overarching non-invasive ventilation really is in the care of our preemies. We started this episode talking about the delivery room, and we’re potentially looking at sending them home on non-invasive ventilation. It’s something that really needs our attention. We need to understand it as best we can, because it is definitely there in every aspect of their hospitalization. So I think it’s just another highlight of why this matters tremendously.

Brett Manley (46:16.744)Yeah, I totally agree. It’s ubiquitous, isn’t it? We do it every day, all day. And if you start to think about the number of hours that babies are spending on non-invasive support, it’s staggering, particularly as we’re looking after smaller and smaller babies. So the onus is on us to get it right.

Ben Courchia, MD (46:32.328)Absolutely. Brett, I want to thank you for coming on the podcast and sharing your thoughts, sharing your expertise and your experience with us on this important topic. We’re looking forward to chatting with you again, and with the other panelists, at Hot Topics in December. We’ll have the links to register for Hot Topics on this episode’s webpage. The articles that Brett has mentioned will be available as well for consultation there on the webpage. And yeah, we look forward to chatting with you in person in DC.

Brett Manley (47:01.544)Thanks for having me, Ben. It’s always a pleasure to be on. I’ll see you in DC.

Ben Courchia, MD (47:05.089)Same. Bye.