#347 -CPAP with Purpose: Supporting Babies in the Delivery Room and the NICU (Part 2)

Hello Friends 👋

In this episode of The Incubator Podcast, Dr. Guilherme Sant’Anna, Professor of Pediatrics at McGill University, joins Ben and Daphna to discuss his team’s work on implementing an early bubble CPAP protocol in the delivery room. Although CPAP has long been considered standard practice for preterm infants, Dr. Sant’Anna explains why intubation rates remain high in the most immature babies and how his group sought to change this pattern.

The conversation reviews the background of the protocol, which began at McGill in 2014, and the cultural shift required to adopt bubble CPAP as the default approach. Dr. Sant’Anna describes the importance of multidisciplinary training, technical details such as proper prong sizing, fixation, humidification, and suctioning, as well as the challenges of sustaining practice change over a decade.

The results of this initiative are striking: lower rates of delivery room intubation, reduced severe BPD, and improvements in outcomes particularly for infants born before 28 weeks. Dr. Sant’Anna also reflects on lessons learned, the global implications of bubble CPAP in resource-limited settings, and the importance of sharing knowledge to improve care everywhere.

This episode highlights how attention to detail, persistence, and team culture can transform neonatal respiratory care.

----

This episode is part of a special three-part series on the use of CPAP, supported by Fisher & Paykel Healthcare. Their sponsorship makes possible the logistical production of this podcast series but does not involve curation, moderation, or influence over the content of the discussions.

Fisher & Paykel Healthcare offer a full neonatal care continuum which helps provide the best start possible to our precious babies worldwide.

Watch the design matters video series and discover what drives the innovation behind their neonatal interfaces https://www.fphcare.com/hospital/infant-respiratory/support/design-matters/

----

Short Bio: Dr Guilherme Sant’Anna is a Full Professor of Pediatrics, Faculty of Medicine, McGill University. He did his medical school and residency in Pediatrics/Neonatology in Rio de Janeiro, Brazil where he worked as a neonatologist from 1997 to 2001. Dr Sant’Anna went to McGill University in 2001 for his PhD studies in respiratory physiology under the supervision of Dr J. Mortola. From 2002 to 2004 he did a fellowship in Neonatal Perinatal Medicine at McGill University. After that, he worked for 4 years as Associate Prof of Pediatrics at the Neonatal Division at McMaster University before moving back to McGill University. Dr Sant’Anna is actively involved in education and has participated and organized several national and international meetings. 

His research interests are to better understand and optimize the respiratory assistance in preterm infants and the use of innovation and new technologies in neonatal intensive care. In collaboration with Biomedical Engineering and Computer Science at McGill University, and multiple international collaborations, he is working on the development of a SMART NICU/HOSPITAL by using wireless technology and advanced monitoring systems.

----

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

Early Bubble CPAP Protocol Implementation and Rates of Death or Severe BPD.

de Carvalho Nunes G, Barbosa de Oliveira C, Zeid M, Leone M, Mardakis S, Remmer E, Boyer J, Hailu E, Altit G, Beltempo M, Shalish W, Sant'Anna G.Pediatrics. 2024 Jul 1;154(1):e2023065373. doi: 10.1542/peds.2023-065373.PMID: 38887808

----

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

The Incubator (00:01.441)

Hello, everybody. Welcome back to the incubator podcast. We are back today for a special interview with Dr. Guilherme Sant'Anna. Guilherme, welcome back to the podcast.

Guilherme Sant'Anna (00:11.8)

Thank you. Thank you for the invitation. It's a pleasure to be here again.

The Incubator (00:15.326)

Yeah, Daphna is here with us in the studio as well. Daphna, good morning.

Daphna Yasova Barbeau, MD (00:18.567)

Thank you, thank you, happy to be here.

The Incubator (00:20.865)

Guilherme, you are a professor of pediatrics at McGill University in Montreal, Canada. You have an impressive biography. You're originally from Brazil. You do a lot of work in research and clinical sciences related to respiratory distress. You do a lot of global neonatology work as well.

Your work was featured on our platform before you were a Delphi speaker this past edition, and you've been interviewed by our friends at the Global Neonatal Podcast, Dr. Shelley Anne Williams-Dakari and Mbosu Sepalu on episode 246, From Brazil to Canada, How Community and Collaboration Can Lead to Change. We will refer people to this interview for more information about your career. Today, we're here to talk to you about early

bubble CPAP. A few months ago, you and your team at McGill published a fascinating paper in pediatrics and the paper is titled Early Bubble CPAP Protocol Implementation and Rates of Death or Severe BPD. You really take on in this study the association of an early bubble CPAP initiative

in the delivery room and its potential long-term effects on the rates of death and severe BPD in very preterm infants. It seems to me, my first question to you is that it seems to me that CPAP in the delivery room is a, or at least was a done deal. It seems like we knew what we were doing and there's no need to revisit anything. Like we know what we're doing. So what prompted you

to say, let's go back to the delivery room and how we administer this first step of NRP, Elcor. Every international organization is adamant that the first important thing of resuscitation is ventilation. And usually that is in the form of CPAP. So what prompted you to say there is room for improvement there in the delivery room?

Guilherme Sant'Anna (02:36.654)

That's a great question, Ben. And that's pretty much what we have done here in Montreal for long time now. We initiated the protocol in 2014. And then it's been more than 10 years that we're doing that. Yes, I agree with you. CPAP in the delivery room is a done deal. We know that we should not.

preemptively intubate babies in the delivery room compared to them on CPAP. However, if you look for the rates of intubation, the more immature the babies are, they're pretty high. They're still high. So although we know that we should try to put them on CPAP, translate that into practice is not so easy for all of us. So one of the motivations

to establish this protocol of early CPAP in the delivery room was to motivate people more and more to try to avoid intubation so quickly, decision to go for intubation in the first minute, second minute of life. The second one is that there is a say that I am a true believer, not all CPAP are equal. And...

The Incubator (04:01.452)

and read the study to find out.

Guilherme Sant'Anna (04:02.014)

we decided to adopt the bubble CPAP system in the delivery room. And most people provide CPAP using the Neopuff. The Neopuff, it's a mask. The advantage is that it can do some PPV and then you just switch to CPAP. However, you put pressure on the face of the baby. And we know that as you put pressure on the face, you can trigger

The Incubator (04:27.782)

security.

Guilherme Sant'Anna (04:29.07)

a reflex, a trigemini reflex that induce pauses or apnea on the baby. The second thing is that you have no bubbling. And we can talk more about that, what is the effect of the bubbling when you have the water, the flow go into the water. But in practice, I can tell you it's quite impressive. We had many babies, extreme babies on the neopuff.

The Incubator (04:38.129)

Thank you.

Guilherme Sant'Anna (04:59.554)

CPAP, the saturation is in the 80s and then you switch you put the bilayer or prong on the bubble the saturation shoots up like in 30 seconds and it's not increasing and we can talk more why this is the case

The Incubator (05:03.931)

Yeah.

The Incubator (05:13.59)

Yeah. You do mention that in the paper saying that bubble C pipe provides pressure amplitude at high frequencies due to the oscillations generated by the water bubbling. so that just the bubbling itself creates that vibration almost.

Guilherme Sant'Anna (05:28.972)

It does. And I think, and in animal models have showed to improve lung recruitment and stabilize unstable or violize. So I think that the pressure is not constant. If you put it on the bubble seep up of five with the water going up and down, you get more pressure. There's a pressure amplitude. And then that happens in a very high frequency.

The Incubator (05:50.823)

Mm-hmm.

Guilherme Sant'Anna (05:58.19)

And the frequency is proportional to the compliance of the lung. That's why lot of people don't know that. The lower the compliance, the higher the frequency because it's a closed system. As soon as you open up the lung and the compliance gets better, the frequency goes down. It bubbles, but it bubbles in a different frequency. Jen Pillow has demonstrated that in Animal Model with Alan Job many years ago in the American Journal of Respiratory and Critical Care.

The Incubator (06:10.173)

you

The Incubator (06:18.193)

Thank you.

Guilherme Sant'Anna (06:27.95)

I think this is the reason why you remove the 3-GMI reflex by putting the prong, you get some positive effect of the bubbling on a high frequency, and then you improve lung movement. So we've been doing that since 2014 in our place, like I said. So we have this bubble CPAP system in the delivery room, now ready to go. And many kids have put them on bubble CPAP in 30 seconds.

The Incubator (06:45.47)

So we have this OCR system in the video.

Guilherme Sant'Anna (06:57.836)

You just suction and then put the prongs and then they start getting the bubble seep out.

The Incubator (07:01.712)

So, so no more neopuff.

Daphna Yasova Barbeau, MD (07:04.507)

Hmm.

Guilherme Sant'Anna (07:05.454)

If the baby doesn't breathe, then you have to do some PPV to initiate, know, trigger the breathing. As soon as the baby is breathing, we put on the, I put on the bow.

Daphna Yasova Barbeau, MD (07:07.409)

Mm-hmm.

Daphna Yasova Barbeau, MD (07:17.179)

Mm-hmm.

The Incubator (07:17.277)

Nice.

Daphna Yasova Barbeau, MD (07:20.147)

That was my question. I wanted to make sure that we all understood when you were switching from a Neopuff. So if the baby comes out vigorous, they get no Neopuff. They go straight onto the interface. Very interesting. I think that helps set the stage.

Guilherme Sant'Anna (07:34.38)

Exactly.

The Incubator (07:34.639)

And yeah, and so the methods of this study and this maybe initiative is very interesting. First of all, I'm very impressed that your initial approach was to put together a multidisciplinary group of people involving neonatologists, respiratory therapists, and nurses. And I think that you were dealing with not just a quality initiative, but also with a potential culture shift in your unit.

So can you tell us a little bit about why it was important, number one, to put this diverse group of people together and what was the obstacle in terms of culture that you needed to overcome as you implemented this project?

Guilherme Sant'Anna (08:15.406)

Yeah, that's another excellent point. It was a, I'm not gonna pretend it was easy. It was a long road. If anybody's listening here and wants to do that, it takes a lot of work, but it's worth it. It took us a year and a half, almost two years of several workshops, training.

Daphna Yasova Barbeau, MD (08:27.591)

Ha

Guilherme Sant'Anna (08:43.648)

and getting all the key players together on board. So when you go to the delivery room, you have a nurse, have a respiratory therapist, you have everybody helping you in this extremely preterm baby. So they all had to be on board, understand why they are doing that. And it's a continuum. So this is the delivery room, but then you move the baby to the NICU and you keep going with the same therapy.

The Incubator (08:49.564)

you

The Incubator (09:06.012)

You

Guilherme Sant'Anna (09:13.894)

We invited experts and people using public IPA for many years, like Jay Wong from Columbia. came here to Montreal, I would say four or five times. And Honey Ali from George Washington, now he's in Cleveland, came here two times. We invited nurses from Columbia to come here and do calls with our nurses here showing how they place the prongs and how they fix the whole system. So I would say we...

We had two cycles of workshop. In the first one with Wong, we about 20 workshops training everybody. And in the second one, about 10 workshops training everybody. You elected champions in your team. So you see people who get more excited and like it, a nurse or respiratory therapist, you over train them and then they train the other ones on a daily basis during calls. So it is a changing culture. It's a...

The Incubator (09:55.515)

Thank you.

Guilherme Sant'Anna (10:12.366)

It was a place I would say the NICU or the Ohio Victoria Hospital used to intubate everybody below 28 weeks. When I came here in 2009, was the standard of treatment. If you were at 28, you got intubated. And then the trials came out. And then that started to shift. And we were lucky because all these trials, they came out between 2000 and 2010, 2012.

The Incubator (10:34.993)

because of the wall.

Guilherme Sant'Anna (10:41.358)

and we established our bubble in 2014. So we got this time that everybody was talking about putting C-POP in the delivery room. And we took the ride and said, well, if we're going to use C-POP, let's use C-POP in this way. So you might ask me why I had the idea to go for this way. And that's the result of a lot of frustration of many different ways that didn't work out.

The Incubator (10:42.05)

We start to...

The Incubator (10:53.123)

Sleep and have a good

The Incubator (11:02.618)

And that's the result of a lot of frustration in many different ways.

Guilherme Sant'Anna (11:08.984)

tried NIPPV and tried intubation and tried many things and the rates of BPG and the success was the same. There was no change. Until one day I said, these guys, they keep publishing very low BPG rates. They keep publishing. don't pay babies in New York and George Washington, et cetera. Well, let me go and talk to these guys, you know, what they do. It wasn't the same for me, you know? So I knew Wonk for a long time.

The Incubator (11:12.462)

It stinks.

The Incubator (11:19.039)

Thank you.

The Incubator (11:35.515)

So I think that's the only one I'm to do. trying figure what's happening. It's it's really sad.

Guilherme Sant'Anna (11:37.678)

But I was never able to really fully grasp and understand this is not just bubble. It's the whole holistic approach on how to deliver the bubble C-pop system. So when I got to understand that, I said, well, we should try it and let's see if it works. Because if it works for them for 50 years and the other guy for 15 years, so why we can't do that? They're not so much.

So different that we have babies, you have nurses and et cetera. So we're not stupid people. if they can do well as well. So basically decided to follow to the dot exactly what they do and got all this training I described to you. Believe me, it's much easier to come with something that, just give that in this way and this is it. It's much easier, but it's many times not sustainable.

The Incubator (12:07.706)

If you can be a great leader in this, it's because you're student.

Daphna Yasova Barbeau, MD (12:29.958)

No.

Guilherme Sant'Anna (12:35.278)

So we wanted something that will be sustainable. So we make a big change. You change the culture. You change the way people see and approach babies in this way to this way. And then this is going to stay longer. If it works, it's going to stay longer. But now the beginning is tough. I went through a lot of times. I almost give up.

The Incubator (12:47.15)

Thank you.

going change my hunger cures, but at the beginning I went through lot of times where I was given up, and gave up.

Guilherme Sant'Anna (13:00.364)

I said to a woman, this is not working. We train people, we talk to people and it just doesn't happen. The next baby that comes, they intubate and et cetera. I said, don't worry, don't worry, don't worry. Start doing it yourself. Do it yourself. The next one that comes with you, you do it and they will see it. And then you do it again and they will see it and then you do it again. So I did. So I started doing it myself. So the next baby that came, was a...

The Incubator (13:12.384)

Thanks.

Daphna Yasova Barbeau, MD (13:14.428)

Hmm.

The Incubator (13:15.865)

Thanks.

Guilherme Sant'Anna (13:28.59)

If I'm not wrong, was a 24 or 25 week that I put an emergency button in the delivery room. Everybody was with the laryngoscope ready to do the intubation. They said, well, let's give it a try. So I remember I said to the team, oh, we'll do the intubation when we get to the unit. And we never intubated that kid for the next 24 hours. And everybody, oh my gosh. people think, oh, this is blood.

Daphna Yasova Barbeau, MD (13:47.943)

Mm.

The Incubator (13:52.377)

It's the of God, this is the name God.

Guilherme Sant'Anna (13:53.634)

You know, this is just baby, you know, this baby was lucky. And in fact, the baby ended up getting intubated after 24 hours. But everybody said, for 24 hours, he was okay on the bubble seat bar. And then the next one came, I was very lucky because the next one came, was a 25 week, I never got intubated, ever. And then I did the next one. And then I think I did the first five or six in the unit. And then one day I saw people doing it.

The Incubator (14:07.642)

because the next one came, was a 25-peak and a

Daphna Yasova Barbeau, MD (14:22.951)

You

Guilherme Sant'Anna (14:23.726)

And I remember I was in the NICU one day and the team came up from the delivery room with a baby intubated, look at me, I'm sorry, I'm sorry, I tried. I said, that's when I thought, now it's working. People really now got the message. And I was also very fortunate and lucky because there was another doctor called Elizabeth Heilow and she was a

The Incubator (14:40.173)

Yeah

The Incubator (14:51.417)

Thanks everybody.

Guilherme Sant'Anna (14:53.864)

ex-trainee from Columbia, New York. So she also knew about the New York bubble C-POP system and she was part of like part amount to help me into this. In fact, she is the one who took over the delivery room protocol. I just helped her. And then she was very much into let's put them on the bubble C-POP. So it is a lot of work, but

The Incubator (14:56.345)

Thank you.

The Incubator (15:05.123)

this.

The Incubator (15:13.241)

She was pretty much...

Mm-hmm.

Guilherme Sant'Anna (15:23.094)

It works.

Daphna Yasova Barbeau, MD (15:25.435)

I love that. want to thank you. think it's so helpful for people to hear how hard it was, right? Because I think exactly like you said, I think there are probably a lot of times you thought, this just isn't going to work. And we all get there when we're trying to make culture change in our units. So it's helpful, I think, to hear those struggles and the things that were very successful. Like you said, you going and you doing it yourself and showing that you believed in it and getting those champions involved.

I wonder if throughout the process you've really learned something though about optimizing CPAP, the way you're putting on the interface, the way you're maintaining pressure loss, things like that, that may help people be more successful on the first few tries.

The Incubator (15:59.051)

So you can still see her.

Guilherme Sant'Anna (16:14.088)

for sure. Wong has said that the more you do something, the more comfortable you become, the better you do it. And this is very much true. If you do something once in a lifetime or once in a while, you never get good on that. So as soon as we started doing that, now I've learned so much over the next 10 years. Because if I may say something about, aside from being

The Incubator (16:15.257)

Thank you.

Guilherme Sant'Anna (16:42.754)

Ventilator or bubble, no bubble is significantly better for RDS. But aside from that, it's the devil is in the details. And many times we in neonatologist, we think, I prescribe CPAP and then you walk away and let people do the CPAP. In this protocol, we didn't walk away, we stayed. We stay with a checklist.

The Incubator (16:50.804)

It's a day off home. It's a good day.

The Incubator (17:05.411)

Peace.

Guilherme Sant'Anna (17:12.334)

And the checklist goes from the right side of the prong size, the right size of the prong. So, and that's a mistake that I've seen many times people putting up a nasal prong that's too small because they want to avoid damage. So they put the smaller one and it should be the opposite. You should put the bigger one for two reasons. One, the bigger one is fixed, doesn't move too much.

The Incubator (17:14.787)

you

The Incubator (17:29.473)

Thank you.

The Incubator (17:35.805)

One of the big ones is that we have too much, and we are less.

Guilherme Sant'Anna (17:39.85)

So have less internal cause of injury. And the second one is that the resistance is the inverse proportion of the fourth power of the radius. So if, and if they're breathing through the nose, right, and if you put a very narrow tube, increase resistance quite a lot. And what people don't realize is that when you apply a CPAP system and interface that with the baby,

The Incubator (17:43.607)

And the second one is that resistance is the

The Incubator (17:55.735)

I think they're a

The Incubator (18:06.711)

I think the first page will be...

Guilherme Sant'Anna (18:09.292)

the flow is passing by. The baby sucks the air in, inspire and expire into the nasal prongs. So the baby pulls the air and expires into the prongs. So if the prongs are too small, too narrow, it's too high the resistance. So increase the work of breathing of these patients. So we've learned that, you you need to put the the bigger prong and then we have learned that you need to have a proper fixation.

The Incubator (18:12.435)

Please subscribe to my channel.

The Incubator (18:27.127)

So we have to look at the dimensions of the fluid that is created by the vapor in the air. And we need to have a proper fixation.

Guilherme Sant'Anna (18:38.168)

How do you fix that the interface is there 24 hours a day or 23 hours a day, not getting off all the time? Because if it keeps getting off all the time, then it doesn't get the CPAP. And of course, we cannot be at the bedside 24 hours. So then we use the Velcro system on how to do the fixation in the lateral and the temporal area. It has to be a U shape. And we're going to talk about that in more details.

The Incubator (18:51.927)

So that leaves the film consistent and not with the fixation.

Guilherme Sant'Anna (19:08.538)

We do talk about that when we do the training. So it has to be a U shape, cannot be a V shape. It needs to be fixed here with a Velcro far away from the septum. Because if you put the prong all the way inside and the cannula touch the septum, you will have septal injury. There's no way. So the only way to prevent septal injury is to be out. So the prongs are not touching the septum.

The Incubator (19:09.238)

Thank

The Incubator (19:22.806)

inside the Canada budget has been, you know, has been a little bit away. So the new, new conventions have made it much, much easier do something about the current budget.

Guilherme Sant'Anna (19:35.49)

We need to have a protocol for inspection and suction because babies are nose breathers. And if the secretion blocking, they go in respiratory failure. You know, it needs to be suction. needs to be suction, many times deep suction because secretion accumulates on the back of the throat, not just here. We need to realize that premature babies, have a very prominent occipital area. So they tend to do that. They tend to flex and block.

The Incubator (19:50.568)

Mm-hmm.

The Incubator (19:56.33)

We need to be faster.

The Incubator (20:05.302)

So you can do whatever you want with your shoulders.

Guilherme Sant'Anna (20:05.708)

So need to put a roll in the shoulders to have the neck now open. So all these details, like you don't put an NG, you put an OG because otherwise you block. You need to keep the humidity and the temperature perfect. So your humidifier, heater humidifier, they need to be at 36.9 or 37 degrees because you lose 0.5 on the way to the patient.

The Incubator (20:11.776)

video.

The Incubator (20:32.711)

Mm-hmm.

Guilherme Sant'Anna (20:33.53)

when the air gets to the baby is 36.5, body temperature. So conditioned air, because if you don't want condensation and you decrease the temperature of the heater, it's going to be, the air is going to be cold. Cold air is going to dry the mucosa and bleed. The major cause of nasal bleeding, it's cold air, dry and non-heated air. So the air has to be warm.

The Incubator (20:49.333)

The Incubator (21:01.269)

Thanks for watching.

Guilherme Sant'Anna (21:03.712)

and has to be humidified, otherwise you start having nasal bleeding. There was a time when we established the protocol. One day I walk into the NICU, we had like three or four kids on nasal bleeding. I said, my gosh, what's going on? And now because of the, and people are debating because of the size of the suction catheter, or they're debating about the prong size. So I decided I walk into the NICU and as I knew that, the first thing I go is I go to the humidifier and the heater.

The Incubator (21:11.541)

I'm and I see you and like two or four kids and it's me. Oh my gosh.

The Incubator (21:20.405)

I'm myself to this. I just want to sleep.

So I had to say that I had pay for the first day of work.

Guilherme Sant'Anna (21:32.972)

And the heaters are 32.5. And so why they are 30? because we're getting too much condensation. So we put it down. So you can't do that because they bleed. So this is the details now that we've learned on the go by errors, by making errors and fixing the errors and learning with people who already been through that. And they knew and they could tell us.

The Incubator (21:36.521)

So this is the T-fail is not that important.

The Incubator (22:02.707)

Yeah, absolutely. And that's so interesting because like you said, the devil is always in the details and it's up to us. It's not always easy. We're pulled in so many different directions to actually stay there and make sure that do some quality control, especially when you have to deal with a change of culture. Another interesting aspect of the protocol obviously is that you had a specified

criteria for bubble CPAP discontinuation. And it says in the paper that it was requiring a minimum corrected gestational age of 32 weeks to ensure prolonged exposure to treatment. You do mention in the introduction, obviously, the mechanism with which CPAP allows for alveolar recruitment and better lung growth. We're going to have on this series Dr. Cindy McEvoy, who's going to talk to us about extended CPAP treatment. But I'm just wondering

about what does your practice look like? Because for us, for Daphna and I in our unit, we tend to go until 32 weeks, but the paper mentions until a minimum of 32 weeks. So can you tell us how long these babies remain on CPAP? Especially when you have these infants who are on double CPAP plus five, 21%. And all the staff is wondering, he doesn't need it. Like, we could get off the CPAP.

Guilherme Sant'Anna (23:14.904)

Yeah.

Guilherme Sant'Anna (23:25.486)

Yeah. If I'm not wrong, in the paper, the median gestational age is 33 or 34 that they stayed on CPAP. So we went above. So the minimum is 32. Currently, I think it's about 35, sometimes 36 weeks that they stay on CPAP. That's another thing we've learned with Wong in New York. There's animal studies showing that the longer you stay on CPAP,

there's alveolar growth and there's increasing protein content. So the lungs grow both ways. It becomes bigger, but the number of alveolus multiply. And there's two or three studies in animals showing that. And then Cindy did that in Ohio, Oshu. And then she did that for two weeks, two extra weeks. And now she had a second paper that just came out in the American Journal.

of respiratory and critical care, medicine, looking for lung function at six months and around one year of age. So showing that not just you increase FRC significantly, FRC doubles in two weeks. And this is compared babies off CPAP well. This is what's impressive. The two extra weeks double FRC compared to babies that are well, not babies on oxygen, not babies not doing well.

The Incubator (24:24.98)

you

The Incubator (24:45.107)

you

Guilherme Sant'Anna (24:52.704)

and kind of triple by the time of discharge from the NICU. And now she's showing that lung function is sustained. Later on, six months and 12 months, these kids have better lung function. So the effect is that by applying this stochastic resonance that comes with the bubbling CPAP, you stimulate. There's a big stimulus for lung growth.

The Incubator (25:07.411)

in effect is that way.

The Incubator (25:16.98)

I'm used to it. I think it's too much when you're broke. I was just saying, when I look at the children, I don't understand why people are going to crush things like I said.

Guilherme Sant'Anna (25:22.094)

I used to say, you know, when I do my teaching in Brazil that I don't understand why people want to rush babies off CPAP room wear. They're fine. What is the problem? You know, it's not intubated. I don't know. So it's kind of strange. People sometimes are afraid to extubate. They don't bother. They leave the baby intubated longer, but they get this anxiety to stop the CPAP and take off the CPAP.

The Incubator (25:34.5)

So I mean, me, it's kind of strange. Sometimes we the best people. We do all the things we need to be able to do. The end is not so to end up showing.

Guilherme Sant'Anna (25:50.51)

So our criteria is that it was, you get to 32 weeks, has to be more than 1.3 kilos. And that's not in the paper because everybody was more than 1.3 kilos. It has to be in room air, 21%. No tachypnea, no gsats, no bradies. When the nurse disconnect to do the cleaning, the baby stay well, doesn't do anything. So it's completely well. And he's now 32 weeks.

The Incubator (25:52.133)

is here because you have to tell me two things. It to be, has to be, more than one.

The Incubator (26:06.579)

Thank

The Incubator (26:17.299)

and he's not a legit boss. So you can talk about it.

Guilherme Sant'Anna (26:20.494)

So you can try him off, CPAP. That was the protocol. Now we don't even try. We wait longer, 33, 34 to do that. So then you try and you take the baby off CPAP. And let's say in the next 24 hours, these babies are having dry Gs, Gsats, and the nurse calls you and say, wow, he's having that, you know. So just put it back. And that's another thing that I don't understand because the biggest...

The Incubator (26:28.135)

Mm.

Guilherme Sant'Anna (26:49.518)

marker that there's still some residual lung disease is need of oxygen, is oxygenation. So you remove something that's promoting lung growth. As soon as put the baby on CPAR, it goes to 21 % nowhere. And then you remove it, and then you need oxygen, and people put low-flow catheter. Why? It's not helping anything. It's just buffering. It's just like masking the Gsat. So now it no longer has Gsat.

The Incubator (26:52.631)

you

So you can use something that's recording on your device. And do it by using your device to help with some of the And then you can use it. And then you can use it to do anything.

Guilherme Sant'Anna (27:18.67)

But you're basically telling him, and the zero lung disease, the lung growth that you need, you do it by yourself because I'm not helping you. So what we do is that we put back on CPAP. So if the baby fails, the winning of CPAP quick in the first 24 hours because he has more lung disease. So we put it back and leave another three, four, five days before we try again. If the baby that some of them, you remove the CPAP and

The Incubator (27:28.146)

So what we do is that we make this. So if the baby fails, the baby of SIGMA, the first thing it knows is it's one of those things. So we don't have anything on this baby for five days. We're going to find it. If the baby gets caught in the middle of the SIGMA,

Guilherme Sant'Anna (27:48.29)

You know, they're fine first day, second, third, and by day five, they start having more brides and g-sats. They're almost there, but with time, they do recruit. So we put them on Bubble CPAP, back on Bubble CPAP 24, 48 hours, and then we try again.

The Incubator (27:50.012)

Thank you.

The Incubator (28:05.682)

Guillermo, I wanted to ask you about surfactant. I'm sure people listening are wondering, well, what about surfactant? Because many babies who don't get intubated might still benefit from the administration of surfactant. How did you navigate this issue? Is your unit mitigating that by using Lyssa, any other form of less invasive surfactant? Or would you have done Insure and would have not counted as an intubation? Can you tell us a little bit more about that?

Guilherme Sant'Anna (28:33.462)

No, we don't. We don't give insure. We don't use Lysa. We use BoboC-PAP. And if it doesn't work, then we intubate and give surfactants. And because when we intubate with pre-med, it's very difficult to intubate, surfactant, and extubate right away. So our major attention is intubate pre-med, intubate the baby very stable in the NICU.

Daphna Yasova Barbeau, MD (28:44.549)

I love that.

Daphna Yasova Barbeau, MD (28:55.047)

Mm-hmm.

Guilherme Sant'Anna (29:03.374)

no desats, easy intubation, give surfactant, put a minimal gentle ventilation until they wake up and then you take them out and actually put to CPAP again. For the babies who go on CPAP 24, 48, 72 hours and end up failing, know, when you intubate and they are too older,

The Incubator (29:06.939)

Yes, sir.

The Incubator (29:16.25)

Mm-hmm.

The Incubator (29:19.921)

Thank

you

Guilherme Sant'Anna (29:30.926)

Usually it's not surfactant deficiency. Surfactant deficiency is more in the first 24, 48 hours because by that time they're already making their own surfactant. So you keep them with the CPAP, the ovulizer open, the ovulizer start making their own surfactant. Usually these babies, as soon as you intubate them, they're fine. It was more like apnea central.

The Incubator (29:35.441)

.

The Incubator (29:42.001)

you can see it

The Incubator (29:50.289)

Thank you.

Guilherme Sant'Anna (29:57.326)

they get intubated 90 % is because of apnea or these ads. So for delayed intubation. So I don't think there is any problem to delay. In the SUPOR trial, if I'm not wrong, 83 % of the babies assigned to CPAP end up getting intubated later in the NICU. So delay, surfactant administration.

The Incubator (30:05.211)

Mm-hmm.

The Incubator (30:08.625)

see the problem today.

The Incubator (30:15.665)

Thanks.

Guilherme Sant'Anna (30:25.486)

did not show any side effect on the opposite. 24 and 25 week are increased survival by not intubating in the delivery room. So I believe that the more immature the babies are, the less invasive you should be in the transitional phase. And so we tried to do the intubation later in the NICU under very well controlled environment. And they say, OK, so you have time to prepare for the intubation. You have time to have the ventilator.

The Incubator (30:32.325)

Mm-hmm.

Guilherme Sant'Anna (30:53.826)

There's not much bagging and all these things are more gentle with the lungs.

The Incubator (31:00.272)

Thank you. Thank you for that. so it's important to mention that the way you broke down your patient population is that you had a pre-protocol period, which is period zero. And then you had three then separate periods where you looked at the evolution of that. And a lot of the babies, it's interesting to see that when we were mentioning surfactant administration, that pre-quality initiative,

you were at about 96 % of the babies were getting it about similar in the first period, but it dropped down thereafter to 85 % and then 70 % in the latest cohort. So definitely were able to get many more babies to do well without needing surfactant. So the time is flying by. And so I think we have to move forward. I want to mention, obviously, the outcomes that you were looking at. The primary outcome of your project looked at the composite

of death before 36 weeks and severe BPD. what you've been able to show is that the number of infants who were free of any BPD increased from 55 to 60 % with lower rates of severe BPD in the later periods. I think it's quite interesting to look at that data because you can clearly see how, I mean, I'm sorry, this is not super scientific, but there was clearly a shift

in your patient population, where in the first period you would look at maybe 14 % to even like 19 % of moderate BPD, 14 % of severe BPD. But it seems that a lot of that population shifted to either no BPD or mild BPD with in period three, about 84 % of the babies having either no BPD or mild BPD and only 16 %

having moderate or severe BPD. So quite impressive results. You also have a lot of different secondary outcomes. As you've mentioned already throughout the conversation, delivery room intubation decreased over time for the overall population. You had a logistic regression model that revealed a significant decrease in the odds ratio for delivery room intubation over time. The number of infants not requiring any intubation within the first seven days decreased from about

The Incubator (33:26.043)

The number of babies not needing intubation went up from 19 % to 40%. There were no differences in mechanical ventilation duration, the need for postnatal steroids. think that's a question people may also ask. The length of hospitalization was the same. Another important question, especially as we mentioned the extended use of CPAP, nor was there any change in the rates of death.

Interestingly enough, also the PDA treatment and late onset sepsis decreased over time. PDA treatment I mentioned, right, over time. And that the impressive thing for me was that in infants born before 26 weeks, they had the most marked reduction in delivery room intubation going down from 96 % in the pre-protocol period to 40 % in period three. You mentioned obviously in the paper that the infants born between 26 and 28 weeks

were the main drivers for the respiratory outcome improvements. And so I think that's important to mention as well. So very, very impressive results. How did your team react when you presented these outcomes, especially because the study took so long? Sometimes maybe it's hard to realize the effect size of the things that you've done. But I'm just curious about considering the culture shift that you were talking to us about earlier, how did they react to these numbers?

Guilherme Sant'Anna (34:48.846)

We presented to them two years, four years and six years of publication. We waited to have six years for the publication, right? To show different epochs. The reason why we did that, because there was some evidence that there's a learning curve. So we want to see how was the learning curve and then if that was sustainable. Because sometimes you do an intervention, things get better, but...

after one or two years, things go back to the way it was before. And we stopped in 2020 because that's when the COVID hit. There was a pretty complicated situation during the COVID with nurses moving and quitting, retiring. I'm sure if I look into the data, 21, 22 is not the same as 20. Now it's probably back to the way it was because of COVID.

The team was very happy. But you know, was something interesting, this question, because they kind of knew. You sense it in the NICU. You see it. You walk into the NICU, you have 20 babies on CPAP, two on NIMV, and one intubated. So that's very common. You walk in and you have 45 babies and 22 on respiratory support.

The Incubator (35:54.432)

okay.

Daphna Yasova Barbeau, MD (36:06.095)

Mm-hmm.

Guilherme Sant'Anna (36:15.758)

And of this 22 in respiratory support, 18 above OCPA. And then they started to see many kids never got intubated and home. And the other thing we noticed is that the number of babies going home on oxygen pretty much disappeared. And had almost no babies going home on oxygen therapy. Basically, the Home O2 program at some point called me, what's going on? I mean, what's going on? Because they're going home with no O2.

The Incubator (36:23.33)

Mm-hmm.

Guilherme Sant'Anna (36:45.134)

So they're going, and we saw many something I've never seen before, we don't highlight that in the paper, no. You have that, very rarely you're going to see a 25-weeker going home at 37 corrected, right? They usually go home at 44, 46 corrected. You see a lot of these extremely, extremely preterm babies, 25, 26, 27 going home at 36 corrected.

The Incubator (37:05.537)

Mm-hmm.

Daphna Yasova Barbeau, MD (37:13.319)

Mm-hmm.

Guilherme Sant'Anna (37:14.446)

on roomware and feed me. One of the concerns that people thought is that by prolonging the CPAP, you're going to affect the ability of these babies to feed. No, not at all. Not at all. As soon as you stop the CPAP, they're feeding in 24 hours, most of them. It's quite impressive because I think they're healthy. They're very healthy. So we do not see that. And there's some evidence.

The Incubator (37:41.431)

Right.

Guilherme Sant'Anna (37:43.726)

not very strong, but some studies show that you can feed babies on CPAP. No, honestly, I no problem with babies on CPAP room air, no respiratory distress, 35-weeker, why you cannot feed on CPAP? New York feed, put them on the breastfeeding on CPAP. But we don't do that in our place. And the reason why we don't do that, because we would have been too much work with the nurses and et cetera. Another culture to change for...

a handful of babies that need that. Because many of them, by the time they get to this gestational age, you can remove the CPAP and they can feed very quickly. it's, you know, many colleagues and you know, some of them who joined us came from other centers and joined McGill, NICU. They walk into the unit a few months later and say, my God, this is unbelievable. You know, because they work in places that

The Incubator (38:14.742)

Mm-hmm.

Daphna Yasova Barbeau, MD (38:37.351)

Mm-hmm.

Guilherme Sant'Anna (38:41.038)

and the kids get intubated and complications and et cetera. Now, of course, it's to a very big challenge for the ones 22, 23, 24-weekers and sometimes 25-weekers. Many of these babies are at one lie and now many of them, especially 23, 24, end up intubated. They need intubation and mechanical ventilation. But the fact that we always...

try them on CPAP, I don't think make them worse. And our survival rate increased tremendously. If you look for the number of babies that died, it was very, very small compared to many other studies. And the severity of the lung disease, whether you call it BPD or not, but the severity of the lung disease was way, way, way lower. Many kids just a bit of oxygen, many kids in bloom where.

by the time they go home. So we stopped seeing these cases that need tracheostomy. We stopped seeing that. So I think the people working in the unit, sense it on a daily basis. And we presented the data. And of course, when we presented the data, it became really exciting.

Daphna Yasova Barbeau, MD (39:56.487)

Thank you for sharing your experience. think people are learning a lot. This is obviously going to be a hugely impactful, even in high resource settings. But I'm curious, you've practiced all over the world with your commitment to global health. How do you think this will change neonatology around the world in less resource rich countries?

Guilherme Sant'Anna (40:25.996)

Yeah, it's not easy, as you know, I go a lot to Brazil for teaching, and I'm a big advocate of bubble CPAP in Brazil, because I think the countries that have less resources, this is even more critical to avoid them going to mechanical ventilation, especially the bigger ones, where you can have a lot of success with CPAP, with the bubble CPAP. But at the same time, to convey knowledge is not

Simple. People need to know what is, what takes to do that, how you do that. They need to know that. And once they know it, then they can do it. And it's easier for companies and salespeople go to these places and convince them that maybe this new therapy or this new machine, this new medication.

now is better and they buy it very easily. Then going into something that's going to take, like I described to you, know, there's going to take time for change. But I've been very successful in Brazil. I would say that so many units in Brazil have changed the bubble C-POP. I get messages every day from them and they just presented in São Paulo four different units from the country, from the small areas that very successful treatment, no more intubation.

everybody surviving. And there's a baby, I talk about babies, 2 kilos, 1.5 kilos that were dying before because they were intubated, which is not our reality. So I think there's a lot of studies being done in Africa and South Asia on the use of CPAP. I think a large amount, a big amount of babies above 1.5 kilos should not die because they get intubated and mechanically ventilated.

Now, if people understand how to optimize the use of CIPAP and the bubble is the simplest and I think the more efficient one.

The Incubator (42:33.06)

Guillaume, we're reaching the end of this conversation. So I want to point to one or two things. Number one, for the people listening to this interview and who are interested in learning more, I highly recommend downloading the supplemental information that is attached to the paper. think that the, like you said earlier, the devil being in the details, you go through every single aspect of that protocol in that supplementary material. I think it's very helpful. I have it printed.

And I'm going to actually share it with our respiratory team. so that's number one. Number two, I wanted to ask you, what is the next step for you and this project? This obviously has been very successful. So I'm just wondering if you could share with us what are the next steps looking like.

Guilherme Sant'Anna (43:19.726)

So locally, we keep going. Every four years, we reanalyze the protocol. We update the protocol, and new people come and get trained. basically, like I said to you, after the COVID, there was some shift, and then we are back. My feeling is that we are back to the same way we were in 2020. The other day, I was on call. just got a 25-week-long CPAP. I never got intubated.

believe on that. I am a big believer of knowledge and translation. So you should not know all that and keep it for yourself. No, you have to tell people, know. And my big desire is to see many other ones doing the same, even better than me. Get it, do it in your place. Your results got better. Oh my gosh, I want to visit you and see what did you do that's better than we're doing here because

together, we're much stronger than isolated. So what we want to do is like, I just got some financial support and we're preparing a documentary on the use of bubble C-POP telling the story from Columbia University, which started doing that in 1973. So it's 52 years they are doing that, Jean Wong and the Hanley Ali experience. I know with the replication in George Washington and Cleveland, a McGill experience.

put in the documentary all the details that I mentioned to you and make it available just so people can watch that documentary 15 to 20 minutes and believe or not believe, but if believe in them, moving to that. Now, because at the end of the game, at the end of the story, what we want is babies getting better. I don't make any money with the bubble C pop companies. I have zero profit from that. I spend money, my own money.

The Incubator (44:52.776)

you

The Incubator (45:07.699)

That's right.

Guilherme Sant'Anna (45:18.894)

people and traveling. So we have zero financial conflict of interest. Zero. So what we want is that, know, like all neonatologists, all neonatal nurses, respiratory therapies, when you walk into the unit every day, you want your baby to get better. So it's, you know, basically spread the information and then it's up to the individuals if they believe, they think makes sense, if they want to try to do it.

The Incubator (45:38.931)

Hey, you bitch.

The Incubator (45:48.691)

That sounds great. we will have potentially more announcements coming your way about this documentary and featuring it potentially at the upcoming Delphi Conference. So stay tuned for that. Guillaume, we were over time, but we could keep talking for many, many more hours. Thank you for taking the time to be on with us today. Congratulations on this impressive, impressive work and successfully implementing a very detail oriented project.

Congratulations and best of luck with the future of this project.

Guilherme Sant'Anna (46:21.294)

Thanks, Ben. Thanks, Daphna. You guys are amazing. So what you're doing is what I just said. You are spreading information to everybody for free. So this is fantastic.