#457 - Are We Rethinking When and How We Give Surfactant (ft Dr. Roger Soll)

When is surfactant "early," and when is it too early, or too late? In this second installment of our two-part series with the Neonatal Resuscitation Symposium, Ben Courchia sits down with Dr. Roger Soll, a leading voice in surfactant research since the 1980s, to trace how our thinking on timing has evolved, from aggressive prophylactic dosing to selective rescue therapy to today's less invasive approaches like LISA and SALSA. Dr. Soll unpacks why head-to-head trials keep favoring less invasive administration over InSurE, and how the rise of "nanopreemies" is quietly pulling the pendulum back toward earlier treatment. The conversation also touches on video laryngoscopy and aerosolized surfactant's unfulfilled promise. A candid, technically rich conversation for anyone who has stood at a warmer wondering whether, and when, to reach for surfactant. Dr. Soll expands on these themes at the Neonatal Resuscitation Symposium, September 10 to 11, 2026, at Indiana University School of Medicine.

Transcript

Ben Courchia (00:00.706) Hello, everybody. Welcome back to the Incubator Podcast. We're back today for a special episode featuring our good friend Dr. Roger Soll. Roger, welcome back to the podcast.

Roger Soll (00:10.116) Well, thank you very much, Ben. Pleasure to be here.

Ben Courchia (00:12.702) We're very excited to have you on. You are coming on as part of a two-episode series that we're doing in collaboration with the Neonatal Resuscitation Symposium. Dr. Edgardo Szyld is a good friend of the show, and he's putting together this phenomenal conference that will be taking place September 10th and 11th, 2026, in Indianapolis. People can find out more about the conference online, they can just Google Neonatal Resuscitation Symposium. We're having on Dr. Charles Roehr and yourself. You are scheduled, Roger, to present this year on early surfactant administration approaches in the delivery room versus the NICU (Neonatal Intensive Care Unit). I guess this is what we'll talk about today.

Roger Soll (01:05.806) Sounds great.

Ben Courchia (01:07.342) The first question I wanted to ask you was, when you were approached for the conference, and obviously there are so many topics, so many different directions you could have gone into, what made you want to really focus on this specific topic of early surfactant administration? Because you've written about it.

Roger Soll (01:27.992) It's an issue that I've been involved in since the beginning of my career in fellowship, with our initial surfactant trials in the 1980s. And surprisingly, we keep generating new evidence and new nuances to inform our practice, and our population changes in ways that make us question what exactly is the right approach.

Ben Courchia (01:59.672) I think that I talk to my team sometimes about this. We're working in a field that is quite unique, from the standpoint that from the moment you train to where we are today, certain aspects of our care will change in every aspect. In the case of surfactant, the medications have evolved, the method of administration has evolved, the patients have evolved. And so suddenly you trained with a certain model and absolutely everything is different. And not to go on a tangent, but in the case, for example, of neonatal opioid withdrawal syndrome, even the name of the thing has changed. It's like everything is different. So I'm just curious, you mentioned you were involved early on in your training, as of today, how have things evolved specifically, and what are the new challenges we have to contend with?

Roger Soll (03:00.708) So, first to your more general point, Ben, it's really very exciting that we can't sit on our laurels and pretend we simply know what to do. I admire our field for continually rethinking this, and not thinking that we had the answers back in the 1980s. To think of all the changes and rethinking of this paradigm that has occurred — let me take you back to the original trials. This is ancient history for some.

We had animal-derived surfactants and synthetic, non-protein-containing surfactants. I won't go into that, but for any surfactant product being tested, two general approaches were taken. One was a more aggressive prophylactic approach, and the other was a selective, so-called rescue approach. The prophylactic approach was pretty aggressive in the early studies, in part because the animal work suggested that you really had to get in there even before the first breath if you wanted to prevent lung damage. So some of the studies looked at very high-risk populations, based on 1980s definitions, usually babies less than 30 weeks gestation, and get in there immediately and intubate them before there were any signs or symptoms, but just based on their risk factors.

The other class of studies were termed selective studies, or the rescue studies, where infants had to have some signs or symptoms of RDS (Respiratory Distress Syndrome) before you considered surfactant treatment. Those two study types sort of went along in parallel, and both were proven to be successful strategies. Where it gets interesting is when we tried to compare them head-to-head.

So we said, surfactant works, works both ways, let's see which is better. In the 1980s, there were a series of studies that compared aggressive prophylactic treatment for infants who were thought to be at risk based on gestational age, versus letting those infants stabilize and treating them only if they had signs of RDS. In those initial studies, prophylactic therapy won hands down. There was less pneumothorax, there was less mortality.

I'll point to myself on this, I was busy saying this is the way to go, based on these early studies. But as you said earlier, Ben, practice changes, the babies change. Two big things happened in the 1990s. One is that our obstetric colleagues were giving more and more infants antenatal steroids. Secondly, we were getting used to stabilizing infants without intubation, using non-invasive approaches like CPAP (Continuous Positive Airway Pressure). How that colored who needs treatment, and when, is an interesting story.

Ben Courchia (06:10.946) I want to maybe start dissecting all that, because there's so much to talk about. When you're making the conscious decision to call this "early" surfactant administration, what is the definition of early? Is it in the first three hours? Is it in the first twelve hours? What do we mean by that?

Roger Soll (06:31.266) If you asked this question to twenty of your guests, you'd get twenty different responses. I could probably define either pole very easily, but not the in-between. Prophylactic therapy really should be defined as therapy that is given when the child does not necessarily have any symptoms of respiratory distress, but is thought to be at high risk based mostly on gestational age criteria.

Selective means, later on you've got some oxygen requirement that is persistent, and I'm going to intubate you. Where you set that requirement will sort of set the stage for what is early and what is late. I don't think "early" necessarily means you'll treat all the babies within an hour. You're saying, I'm going to treat some select group of babies with a certain constellation of symptoms and signs earlier or later, based on FiO2 (Fraction of Inspired Oxygen), respiratory distress, and other issues like that. I think that setting a low criteria, where you will treat within the first hour or so, probably is truly early.

Some authors have suggested even an "ultra-early," or very early approach, and I would define that as not prophylaxis, but immediately after birth, in the first 15 minutes or so, when there are some signs of respiratory distress. For example, if you're in the delivery room, Ben, and you say, "I've got to slap CPAP on this baby, I'm going to put the sat monitor on, I'm going to give a little oxygen," that's sort of different than prophylaxis, isn't it? That's saying, I've watched this baby for a short period of time, this baby has some very early signs of distress, and I'm going to aggressively treat. That might be considered ultra-early, very early, within the hour.

Saying, this baby's developed an oxygen requirement of greater than an FiO2 of 0.25, 0.30, that might be early. A more conventional approach would be waiting for an oxygen requirement above 30%, 40%, and that would be selective. We no longer think about timing on that, that's really just more selective therapy, and that can occur anytime in the first six, eight, twelve hours.

Ben Courchia (08:56.471) I think there are definitely two categories. There are the people who go to the delivery room with surfactant in hand, with the premeditated intention of saying, if certain criteria are met, I'm going to give it. And those who say, when we come back to the NICU after stabilization, if needed, I'll consider surfactant administration.

Roger Soll (09:17.476) That's an important point, because I would argue that you should always be ready to give surfactant in the delivery room. That's not to say you should do it, but obviously some babies are going to require intubation in the delivery room, and I think the earlier you're prepared to give it, the better for the baby, unrelated to what exact policy you set.

So the idea that you have surfactant available in the delivery room, and a method of getting it to the babies, I think is an important policy guideline decision for every unit, no matter what you decide.

Ben Courchia (09:50.552) We were talking a bit earlier about risk stratification, and you mentioned that in the early days of prophylactic treatment, the risk stratification was kind of a little bit coarse, and basically just looking at gestational age. We now have such a diverse population of patients, going from, I guess "nanopreemies" is the new, in-vogue term, but we really have our very tiny babies, the 22-weekers and the 23-weekers. We still have our 26, 27, 28-weekers, and they're dramatically different babies. Does that mean we have to have different approaches for different gestational ages? How do you approach this? Do you have different categories that you look at?

Roger Soll (10:34.924) That's a great question, and the uncertainty is rife, obviously. A couple of things, just to extend the story.

One, the prophylactic approach I discussed from the 1980s falls by the wayside with more current trials of delivery room stabilization, in the context of being able to give CPAP and having babies adequately treated with antenatal steroids. So you have the big NICHD SUPPORT trial. You have Mike Dunn's trial, done through the Vermont Oxford Network, telling us that aggressive prophylactic care in babies above 25-26 weeks is probably not the right approach. It's probably an over-treatment of infants who can be stabilized on CPAP and moved out of the delivery room and treated more selectively. In those studies, there's a slight tendency towards less lung injury and chronic lung disease in the infants who are not aggressively treated. So that's a 180-degree turn from the interpretation from the 1980s.

So there we have it for the babies who've been in trials over 25-26 weeks, fine. But what you're asking me, Ben, is wait a second, we have a whole new category of infant that we're handling now, one who is much harder to stabilize early on CPAP, one who may well benefit from early intubation, but is untested. We've got lots of very thoughtful approaches coming out of the Tiny Baby Collaborative, coming out of Iowa, but few trials. And yet we're beginning to think, this population, which we're now pursuing with their families, if chosen, what is the right care? I think the pendulum is now swinging a little bit back towards the possibility of prophylaxis.

Add another wrinkle to it, we have other ways of giving surfactant which may allow us to maintain the babies on less invasive support.

So, what happens in the world of LISA, Less Invasive Surfactant Administration? What happens in the world of SALSA, Supraglottic Airway Surfactant Administration? There's a gray population there, probably not the 22-23-weeker, but maybe the 25, 26, 27-weeker, who can still benefit from sneaking in there, getting surfactant in, so they're surfactant-sufficient, but not winding up intubated and exposed to positive pressure ventilation and all of our clumsy approaches to assisted ventilation.

Ben Courchia (13:16.845) I think this is really creating a much more nuanced picture. You addressed this issue of surfactant administration, there's been lots of conversation about the merits of a less invasive method of delivering surfactant, then followed up by a question of, well, how have we compared this? The conversation has been around the fact: should we compare less invasive to InSurE, or how do these studies need to be designed? And then, on top of that, for which patients? So how do we navigate this? It seems like a minefield of study design and patient population. I'm curious what your heuristics are on how to get through that.

Roger Soll (14:19.726) One person's minefield, I guess, is another person's candy store. I see it in a much more positive view, wow, we've got all these interesting and effective approaches which I need to tailor to my own resources, service, and approach. Nuanced, yes, but I'm less concerned, I think it's very promising.

For example, I think people should be considering LISA as a routine approach. You mentioned the different study designs, there are two major study designs. One looks at LISA sort of head-to-head compared to other approaches. So if a baby reaches a certain criteria, for argument's sake, let's say an FiO2 of 30%, or 0.3, I'm going to either treat with InSurE (Intubate-Surfactant-Extubate), intubation, surfactant administration, and extubation, or I'm going to give LISA, thin-catheter administration. Same identical indications at that time. I think of those as head-to-head comparisons.

There are also studies that say, wait a second, LISA's unique, it allows me to sneak in there early. I'm going to compare these two approaches, and they're not going to happen at the same time. I can sneak in and give LISA early on with less disruption, and compare it to more selective, later treatment, usually with InSurE. What surprises me, Ben, is that even when we compare things head-to-head, LISA wins. There are signals of less lung injury, less chronic lung disease, even when we compare InSurE to LISA. And you sort of stand back and say, wait a second, neither of them is truly less invasive, I have to still do a laryngoscopy, I need to pass a tube past the vocal cords. So what's with this "less invasive" talk?

What's the difference, and why the size of the tube? In fact, it's easier to pass a bigger tube than a little piece of linguini past the vocal cords. So why? My only pet theory on this is that we don't really do InSurE well, we intubate, we give surfactant, and then we delay on extubation, and we have a certain period of time where we're giving positive pressure ventilation to these kids. Maybe it's just minutes more, maybe it's hours more.

Ben Courchia (17:08.624) Three or four hours sometimes.

Roger Soll (17:18.596) And I don't think we recognize just how deleterious positive pressure ventilation is, how poor we are at gauging the infant's needs, and probably, even with our best efforts, how damaging it is. Animal models tell us that. But somehow, in our own personal efforts, we think the babies need these things, we think we're doing something good, we're probably causing harm. So I think poorly done InSurE, which is probably what most of us do, fails compared to LISA.

And then the minefield question comes up, so maybe if I did InSurE right, what would be the difference? Can't be the size of the tube, right? If I truly put a regular endotracheal tube in a baby, in fact, and pulled it out immediately, I'm hard-pressed to understand why that would be better than using a thin catheter. But I think because InSurE allows us a window to give positive pressure, we cause mischief. LISA wins in the trials that have been done.

Ben Courchia (18:18.641) Very interesting. This is more of a commercial question, and I have no skin in this game, but obviously in Europe, I believe they've designed catheters specifically for administering surfactant in a less invasive way, while at least for me in the US, I still have to jerry-rig something to make it work. Do you think this plays a role, or not necessarily?

Roger Soll (18:44.356) I think you can adequately deliver LISA without a specific instrument, but I think it's preferable. I've been involved a little bit in discussions when they originally designed this. It's nice to have a vocal cord guide on it, to see where you're at, to have a colored catheter which you can see easily through secretions, etc.

So it's a small benefit. If I had a choice in the delivery room, I would choose to use that tool. But I don't feel bad about what we do in terms of just grabbing any old catheter and trying to measure it right. There are also people who just use an angiocath, I'm busy talking about thin catheters, but that includes the work that was done, mostly in Australia and New Zealand, with MIST (Minimally Invasive Surfactant Therapy), which just used a big angiocath directly to the syringe and instilled it.

Ben Courchia (19:43.535) I put my MacGyver jacket on when I have to start creating my little apparatus. I kind of enjoy doing that.

Roger Soll (19:51.404) Exactly. It's the roots of neonatology, right?

Ben Courchia (19:55.418) Still, since we're talking about equipment, obviously since the early '80s we've had different options available to us when it comes to surfactant. We have synthetic, we have animal-derived. Does that make any difference? Not superior in terms of product, but in terms of how do we approach early surfactant administration, based on the data.

Roger Soll (20:29.924) Most of us are using animal-derived surfactants at this point. The research efforts are still ongoing, there are some fascinating new products, dry-powder synthetics that are being developed, that frankly defy my understanding of the normal physiochemistry of surfactants. But for our practice, we're using animal-derived products. All the studies have been done with animal-derived products, pretty much, so all the literature I've been discussing comes from that. Whether or not there's a better product, I do think there are some advantages, perhaps, especially with the initial dose, to be able to give 200 milligrams per kilogram of phospholipid. Products that can deliver that, I think, are probably preferable, especially because they have lower volume. People have been turning in that direction. But, fortunately, the research efforts are still very much ongoing, and there are no doubt new products on the horizon. One thing I haven't mentioned is aerosolization. It's the holy grail, I suppose, if we all sat back and imagined what we would love, but it really isn't there. There is no product that has proven as successful as some form of intratracheal administration. So that still remains in the realm of research and isn't ready for practice.

Ben Courchia (22:00.176) We wanted so much, and yet.

Roger Soll (22:01.978) Of course. It's such a beautiful idea, but in fact it always takes time, time away from holding, and other aspects of stabilization, and it just doesn't quite seem as effective right now. So we've got some nice, easy, less invasive ways of administering good old-fashioned intratracheal surfactant. I think that's still where we're at for our practice.

Ben Courchia (22:25.211) Which brings me to my next point, since we're talking about equipment and the tools available to us. I think one of the big aspects, obviously, is methods of respiratory support. We were talking earlier about the historical, natural course this discussion has taken over the years, and I think the tools we have to ventilate patients have changed dramatically. But we've also gotten so good at it, I feel like today we're so much better at managing a patient on non-invasive support than we were, say, 20 years ago, just because these tools have been out there longer, and we've been tweaking, experimenting. Do you believe that the evolution of ventilator technology, plus our ability to ventilate patients well, has made this conversation about surfactant a little bit more optional than it was in the past?

Roger Soll (23:26.958) It is interesting, and clearly the efficacy of the selective approach speaks to your point, namely, we don't have to rush in prophylactically in some of the somewhat bigger babies, and we can be very adequate in our stabilization on CPAP. Smaller babies, as we discussed previously, probably a different story, probably do need more invasive support.

The unknown question is whether or not, even with our much-improved, less invasive care, sneaking some surfactant in there early is an advantage. It may be, it may be synergistic. It may be that we prove we can stabilize well just on CPAP, and that's a compliment to our nursing staff, right? That's a much harder thing than just taping a tube in place. But all of our units have developed that skill, and kudos to them. Can we improve it with a little less invasive surfactant, and then restabilizing on CPAP? Probably, yes. At what cost? Is that a universal issue? Is that for low- and middle-income countries? All good questions.

Ben Courchia (24:39.974) The work that's been done on the administration of early bubble CPAP is super interesting. I think this is also probably something that's going to favor a specific population. But the discussion, as you're probably alluding to, of having ventilators in the delivery room, where babies are no longer just managed non-invasively with a T-piece but with a more sophisticated form of ventilation where tidal volumes are better controlled and so on, probably will allow for better stabilization, but again, as you said, it's a huge cost.

Roger Soll (25:16.344) The other technical issue we haven't touched on is that for any of these procedures, since we're still talking about an intubation of sorts, is the use of video laryngoscopy, which again I think in high-resource settings is probably a major improvement. There are so many issues that go into that, including the fact that with our less invasive approaches, we have fewer and fewer of us with good intubation skills. So the teaching of those skills, the ease with which we do the procedure, the lack of trauma associated with it, probably means this becomes a part of our care as well.

Ben Courchia (25:58.757) Why do you think — some people might press you on that. Some people might say that from an educational standpoint, it's very valuable, because you no longer have to step away from the field to let a trainee peek at the view. But there are many who would say, it's a little bit of a different skill, you cannot do video-guided laryngoscopy the same way you do direct visualization, it's a little bit of an adjustment. And some people might say, I'm comfortable with one skill, I'm not really interested in learning another. Do you think it's important that this transition happens in our field?

Roger Soll (26:36.676) That's cute, Ben, you're talking to an old man here, right? Who loves to brag about how, in my youth, I could intubate with my eyes closed. Let's dismiss that. The 21st century is going to involve using these technologies and learning how to use them. And as you pointed out, first of all, for training I think it's really going to be essential, and then for the rest of us. I think there are good studies to suggest that we can be quicker, smoother, more effective if we do learn that skill. There are costs. And I'm not saying everyone should assume this is their first priority, but I'm pretty confident this is the way things will be five years down the line. And that's from an old man.

Ben Courchia (27:24.466) Appreciate you weighing in on that. Roger, we're getting to the end of our conversation. I wanted to know, if we wanted to bring this home, I think the topic we addressed early on in this conversation was obviously a risk-stratification approach in the delivery room: who is going to be this baby in front of me in just a minute? While the data is obviously very dynamic, as of today, when you enter a delivery room, beyond the NRP (Neonatal Resuscitation Program) set of questions that people recommend you ask, how do you approach a baby? What are the things you look at? Because, like you said earlier, we could look at surfactant administration driven by an FiO2 requirement, but that's probably a little bit reductive. A more global picture might be more accurate. What is the Roger Soll method for risk stratification?

Roger Soll (28:19.928) Roger Soll hasn't been in the delivery room in five years, Ben. I'm not going to dodge it too much.

Ben Courchia (28:22.771) You can't escape. Let's assume you have.

Roger Soll (28:28.63) I'm still strongly driven by gestational age in terms of when I'm going to be prepared to have a low threshold to intubate. So this whole new baby, the 22-, 23-weeker, I really think you have to be prepared to say, I have a low threshold for considering failure and the need for intubation. And I also believe any intubated baby needs surfactant at that time. So the act of intubating, and I guess I'm flipping the script here, Ben. I've talked a little bit about intubating to give surfactant. Now I'm talking about intubating because you need respiratory support. And what I'm saying is, that baby needs surfactant.

Ben Courchia (29:06.887) You cannot get away with a baby that's on SIMV (Synchronized Intermittent Mandatory Ventilation) on 21% and say, well, they're on 21%, they don't need surfactant. The mode of ventilation trumps the FiO2 requirement.

Roger Soll (29:14.232) No. So you intubate. Exactly, you intubate in the delivery room, that's another reason you should be prepared to give surfactant.

I know some people will want things like, "I'm going to check tube placement, I'm going to bring the baby up to the unit." I think that's a mistake, it's a discussion we can have, others will disagree with me on this, but I think intubation and surfactant treatment go hand in hand in this population. And I think intubation is much more likely in the small baby. In the bigger baby, I do understand getting away from prophylaxis per se, and then I'm hearkening back to my original definition: just intubating and treating based on gestational age.

For babies around 25 weeks or less, let me restate that, I would consider early criteria, FiO2s of 0.3, and if stabilized on CPAP at an FiO2 of 0.3, I would consider some of the less invasive approaches. SALSA, I think, is an approach, not for most of the high-income countries we're talking about, it may be something for community hospitals, it may be something as we pursue research in low- and middle-income countries. The other things you're alluding to, we have more tools to judge respiratory distress, like ultrasound, but that's again more for the selective treatment approach, probably in the bigger baby, where there are multiple causes of respiratory distress where you might want to differentiate. But I think that might be a bit of overkill, because surfactant doesn't hurt, even in things like pneumonia. So I'm not so worried about that.

Ben Courchia (31:00.887) That's absolutely true. And to be perfectly complete, we've talked mostly about premature babies, and there are very specific clinical scenarios in which the administration of surfactant is guided by different principles, which is a subject for a different time. Roger, thank you so much for sharing your thoughts, and giving us a little bit of a sneak peek at what will be discussed at the upcoming Neonatal Resuscitation Symposium. Again, the symposium will be taking place September 10 to 11, 2026, at the Indiana University School of Medicine in Indianapolis. You guys can register at medicine.iu.edu, or you can just Google, like I do, Neonatal Resuscitation Symposium, and you'll be directed to the registration website. And if you're interested in submitting an abstract, there's an opportunity for that as well.

Roger, thank you so much for being on the podcast again. Thank you.

Roger Soll (32:01.091) Thank you, Ben.