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#035 - 👩‍💼👨‍💼 Dr. Jennifer Beck & Dr. Christer Sinderby


Jennifer Beck and Christer Sinderby on the Incubator Podcast

We are very excited to welcome Dr. Jennifer Beck and Dr. Christer Sinderby on the podcast this week. This husband and wife couple co-invented and pioneered one of our most favorite modes of ventilation: NAVA.


Dr Jennifer Beck's Bio: Dr. Beck obtained her MSc and PhD from McGill University and studied extensively the function of the human diaphragm – the most important respiratory muscle. Dr. Beck developed a method to accurately measure the electrical activity of the diaphragm, a signal representing the output from the respiratory centres “respiratory neural drive”. This technology is now used in the critical care setting to monitor patients and to control mechanical ventilation. Dr. Beck is co-inventor of the “NAVA technology”, and has published numerous papers (>75 publications) on the topic of control of breathing and patient-ventilator interaction. Dr. Beck’s current work is focussed on new ventilation methods for preterm newborns (“Helping Babies Breathe Better”). For this work, she received the inaugural “Angel’s Den” and GHIA awards in 2016. Dr. Beck holds 17 patents which have been assigned to either University of Montreal/McGill University or St-Michael’s Hospital.


Dr. Christer Sinderby's Bio: Dr Sinderby’s work focuses on control of breathing during mechanical ventilation in acute respiratory failure. In addition, he has physiological interests in lung protection, non-invasive ventilation, monitoring and decision support during mechanical ventilation. Dr. Sinderby also does research on new techniques and methods to support the breathing of critically ill patients. Dr. Sinderby holds over 25 patents on this topic. He is the inventor of Neurally Adjusted Ventilatory Assist (NAVA), a ventilation mode that is FDA-approved and commercially available since 2007 and used in intensive care units in over 40 countries around the world.


If you woud like to get in touch with Dr. Beck or Dr. Sinderby for questions or potential collaboration, they can be reached at:


Please see below some resources that Dr. Beck and Dr. Sinderby wanted to share with our audience:





DISCLOSURE: Drs. Beck and Sinderby have made inventions related to neural control of mechanical ventilation that are patented. The patents are assigned to the academic institution(s) where inventions were made. The license for these patents belongs to Maquet Critical Care. Future commercial uses of this technology may provide financial benefit to Dr. Beck and Dr. Sinderby through royalties. Dr Beck and Dr Sinderby each own 50% of Neurovent Research Inc (NVR). NVR is a research and development company that builds the equipment and catheters for research studies. NVR has a consulting agreement with Maquet Critical Care.


 

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


SUMMARY KEYWORDS

babies, catheter, signal, nava, breathing, patient, apnea, ventilator, diaphragm, breathing pattern, people, adults, synchrony, put, pressure, synchronize, feel, neonates, hear, technology

SPEAKERS

Daphna, Dr. Jennifer Beck, Ben, Dr. Sinderby


Daphna 00:00



Ben 00:52

Hello, everybody, welcome back to the podcast definitely what's going on today?


Daphna 00:56

Nothing. We have a we have guests in the house. So you you you can see our listeners can't see. But I'm recording from my daughter's pink unicorn room today. So it's bringing a little extra joy to my morning.


Ben 01:13

You are a unicorn person literally,


Daphna 01:14

it's all literally butterflies and unicorns in here.


Ben 01:17

I feel like if we let you decorate our office, it would be all Disney stuff and unicorns. Am I wrong?


Daphna 01:25

Well, you know, I'm sneaking in the touches to the new call room.


Ben 01:28

I see that I see that. It's almost as if the clock and like in Sketch are inspired by by you, you know? Yeah. You


Daphna 01:36

mean the pediatric?


Ben 01:38

Whenever he Yeah, whenever he does the pediatric pediatric team, it's always like a headband with unicorns, stickers all over the place. Man, no, but like what you've been up to. So what do you think to share with our audience?


Daphna 01:55

Well, I mean, we just we are staying busy. We're staying busy. What about you?


Ben 02:02

Not much. What have I what have I been through these days, I have actually been spending way too much time trying to get more episodes of my favorite TV show. And it's called the repair shop. It's a show by the BBC. Yeah, it's fantastic. I may have talked to you about this already. Now I know. It's basically a repair shop. And people bring their family heirlooms that are sort of old and broken. And these artisans just repair them and restore them to life. And then they present them back. You present them, they present them back to the families. And sometimes it's like a music box that they haven't heard since they were kids. And now they suddenly hear again, the music they heard from their childhood. It's phenomenal. Yeah, Netflix had like two seasons. And then they stopped carrying the show. And there's like seven or eight seasons altogether. So now, I was working on getting a VPN so that I could pretend like my connection from South Florida is actually from the UK, so that I can log on to the BBC website where I can then


Daphna 03:02

watch your show. You're sneaking into the BBC website.


Ben 03:05

I had to sign up for a TV licence in the UK so that I could pretend it's just I haven't been spending way too much time. But guess what, I have access to the BBC iPlayer. And I can watch my favorite show now. So there you go.


Daphna 03:19

I'm happy to hear that. Is anybody ever disappointed after the repairs?


Ben 03:25

No, no, they're very, very good. I'm assuming if they were they would probably be edited out. But no, the people on the show are just so freaking good. So good. It's it's it's my favorite show on TV.


Daphna 03:37

Very cool. Very cool. All righty.


Ben 03:40

So should we introduce our guests


Daphna 03:42

please?


Ben 03:44

Our guest today are Dr. Jennifer Beck and Dr. Krista Cinder V, which if you're like me, you may these names may not ring a bell but they are fascinated. That's exactly right. So Dr. Beck obtained her master's in science and PhD from McGill University. She studied extensively the function of the human diaphragm and she is the CO inventor of Nava technology. And she and she has published numerous papers on this particular topic. Dr. Beck's current work is focused on new ventilation methods for preterm newborns, helping babies breathe better, for which she received the inaugural angels then and g h i A awards in 2016. Dr. Beck holds 17 patents which have been assigned to either University of Montreal McGill University or St. Michael's Hospital. And Dr. Christopher Cinder B is Dr. Beck spouse, and His work focuses on the control of breathing during mechanical ventilation and acute respiratory failure. In addition, he has physiological interest in lung protection, non invasive ventilation monitoring and decision support during mechanical ventilation. Dr. Cinder B also does research on new techniques and methods to support the breathing of critically ill patient He is the CO inventor of Nava as well and holds over 25 patents on this topic. Dr. Chris Larson to be Dr. Jennifer Beck, thank you so much for being on the show with us this afternoon. Definitely want to get started.


Daphna 05:14

Yeah, well, like we were disclosing to you I mean, admittedly, and Ben and I, are Nava fans, right? We trained with Nava. We really like using it. But we're hopeful that you can tell our listeners kind of, in your own words, a little bit about the technology, how it works. And then maybe we can work backwards about how you guys worked, worked through the technology. But first, just to introduce it to the listeners.


Dr. Jennifer Beck 05:46

Do you want to start? Well, you can start I'll fill in what's missing?


Dr. Sinderby 05:49

Yeah, so the technology really started with the problem problems. So patient ventilator synchrony, like it was really the thing about trying to start a ventilator when the patient starts inspiration. And to start with when they end their inspiration, that was really the beginning of it all. So the thing started with that we try to use the diaphragm activity, to see if we could start to stop the ventilator. And at the same time, it was vav had just come out. So proportional assist ventilation had just started. And that was kind of the personality part of it. And of course, since we have the brain signals that they come at, you want to breed, we thought that it's probably a good way to give you an assist that is proportional to your own effort. And which in this case, then we're for the adults kind of competitive with pa V, I will call it but but when it comes to the to the neonates and to infant babies, I mean there is no below six kilos, you cannot use pap. So after. So in the lower range like you, you get to the point that we were alone in that area. So that turned into be like a, an area of I say would say physicians and respiratory therapists and nurses that were much more interested in the technology than they were in the older groups, because first of all, you put catheters inside the babies all the time. Second is the like the nasogastric tubes, I mean, the feeding tubes, yeah. And then once the feeding tube is in, that means you have everything you need to run the system. So in this case, it turned into be like a nice path forward. And as I'm saying, like the the problematic thing with babies is that you you have no feedback at all really like we had some experiences where we looked at babies that looked like they were struggling and breathing and whatever we put down the catheter and probably you have seen it too. There is no diaphragm signal, the only thing they are doing is just fighting the ventilator trying to breathe out when they when the ventilator is pushing air in. So if you had an abdominal kind of like recording of EMG or EDI, it would be seeing that the patient in this case would be actually fighting the ventilator all the time and never do an inspiration because the air that is blown in this too much for them and at the wrong time. So so there is that's that's the background, I will say like the can I can add


Dr. Jennifer Beck 08:29

a few things. Sure. So he alluded to this, but didn't specifically say the word monitor. So it's the first time you can actually monitor the breathing signals, as Mr. Cole did right at the bedside, not only for the asynchrony, but also for the apnea. Because when you have people always talk about apnea, but nobody really talks if it's central, or if it's obstructive especially during non invasive. So when you have a true flat VDI that tells you that their baby is having a central apnea. And so from a monitoring point of view, we now can characterize the neural breathing pattern and look at things like patient ventilator asynchrony in a conventional mode, but we can also look at how the breathing pattern changes, especially the the app knows with feeding methods or kangaroo care, or the caffeine administration, all these assumptions that have previously been made about whether or not something will reduce apnea or make it worse. Now you have a tool at the bedside to evaluate that. So it's it's the control the ventilator but also the the monitoring capability. And of course for the for the Naveh technology controlling the ventilator is it seems to be very successful for non invasive applications. Because when you have leaks, it's very hard to synchronize a ventilator and using the EDI signal die from electrical activity. It's sneaky. adequately independent and not affected by the leaks from a synchrony point of view, obviously, if you have a leak, the delivery will be affected. And you may have to adjust how much you're giving. But from the synchrony point of view, it's, it's also the problem.


Ben 10:15

Right? So to summarize a little bit for the audience, obviously, we're talking about about this novel catheter that is introduced a bit like a feeding cat catheter, as Krista was mentioning, and and basically sit in and around the diaphragmatic area to pick up on diaphragmatic activity. And that can basically synchronize with the ventilator. Now, for the audience who's not really using novel, can you can you tell us a bit? What's this novel level that everybody's afraid of touching when they don't really know? What you're signing out the patient's another?


Dr. Sinderby 10:49

I think, I think you like when we started this, which is kind of like back in 2000, or something like that, like, I think the markets was the first ventilator with never was out there, like in 2007. And that was only for invasive ventilation. And the, the thing we had to set it up like was that how do we deliver assist? Are we going to say that we deliver pressure? Well, we couldn't, because with naveI, it's kind of like the pressure is proportional to your effort? Are we delivering volume? Well, we could say that, but then you have leaks or whatever. So we can't deliver volume either. But we can still delay delivery proportion. So what is it we're delivering with? Well, it's this microvolt signal that is like the, the if you think about like a like a quarter or less than a quarter, that's like the area that you pick up signals from like, it's, this is micro volts segments, they're very, very small. And it's in a very electrical busy environment. So there's a lot of processing and filtering involved and the diaphragm is moving, and we have to follow. But the thing is that once we learned to do that, we had a signal that is in every patient, very reproducible, but between patients, anatomical differences, and so on, make make it different. And that's what makes it difficult, you can't just use the electricity by itself, because what is 10 micro volts in one baby or one adult could be five micro volts in another and could be 50. And yet another there is a, there's a bit of a range, I would say that the 75 80% of patients will have same activity or similar is very similar activity. And then you could actually target just activity, but for the ones that fall outside, it's a bit of a problem.


Daphna 12:44

It's so interesting to hear you guys describe really the mathematical process, because that's what we kind of see at bedside like you can see when the babies are working against the ventilator, or they're, you know, they're just don't have enough effort to sustain, you know, the, the minimum amount of support that we're giving them. And then when we are able to support them a little bit better by using different, you know, set novel levels, we see those kind of microvolts the EDI guys change. And so it's really interesting to see that in real time, and then look at your patient, and you can see that they have improved comfort. You know, we've also found that we are able to use, like you said, even if we're not using novel, even if we don't have it on for some of our babies like that we recently take off Nava, and we leave in the catheter, we're able to see those that monitoring, we're able to use it as a monitoring device, even if we're not using the novel technology to synchronize with the patient. So I you know, I think we use the tool both ways in our unit, and we really like it. I think you've used the term, specifically personalized ventilation. And I think that really helps people understand it, because it's using the feedback that the baby is giving through the diaphragmatic impulses. So I hope that I hope that clarifies things for some of our listeners who may not have ever used the technology before. And I was wondering about your thoughts about the best kind of type of patient or patient populations that you had intended and you know, not to be used for obviously, you said, you know, your work. We were trying to fix a problem that we found in the in little babies in neonates because there was a hole, you know, in our equipment, really, but in the NICU specifically, I don't know if you have any thoughts about the best patient.


Dr. Sinderby 14:57

Could I just go back to the monitoring side that you mentioned before there, and I think that it's, it is like, as you say, like there is a lot of things that you, when you see the baby, I mean, you see the baby moving, you'll see the abdomen moving, you'll see the chest moves and so on. You can think that they are in distress, which you are probably right when you see them. The I think you can judge the distress situation. But you cannot really say why. And you cannot say that say what you when you do something. And I think that's Jennifer alluded to before, too, that the monitoring, therefore is the kind of like important, and I think that if you if you make it to a point of sounds maybe pretentious, but I say like I mean, to us, it's kind of a little bit that is it's, as you see straight into the respiratory centers of the patient. I mean, it's the it's the respiratory centers that we're watching. I mean, it's, it's, it's nothing else, that's the true signal. We did a very interesting study just recently where we had respiratory like bands around the abdomen and the chest wall. And we were doing like an IPPV with very high pressures. And, believe it or not, but I mean, you push the air in with the NIT TV, chest wall doesn't move when it's unseen when it's when it's unsynchronized. But when the baby takes a breath, it's a huge deflection in the chest wall. So when you pump the air that we think so that that was up to 2527 centimeters of water. I mean, it's like high pressures. But it all leaks away and probably works more like an asynchronous High Flow nasal cannula, I would call it the so it blows off co2 rather more than than anything else. And and I think that that's clinically that word you have the thing that if you put down and have a catheter and you actually learn to read the signals from the respiratory centers, and you know, control the breathing a little bit, I think you can take out and then they want this amount of information that is way more than I mean, we are researchers.


Ben 17:06

This is why this is important because for neonatologist, there's this fear right of of failure of motor ventilation. Right. I mean, for us, for Daphna and I we feel like Nava is helpful for babies who are intubated. But for us in our NICU, where we found a tremendous use for it is obviously in our excavated population, because of exactly what you're mentioning where for the first time, you're able to synchronize with the patient in a mode that was until then never synchronized with the baby. And and that makes a huge difference. Also, we know that babies were excavated to an IMV or some form of non invasive mechanical ventilation, they could do better but the ability to have a catheter to measure EDI and work of breathing all the way through even when they're coming off of Nava, and to see even on CPAP that while they're doing okay, this is this is, in my opinion, a game changer. Now, as we're talking about this, I mean, the question that I've always wanted to ask you is I know initially, obviously, you think of adult patients and I feel like Nava is a tremendous tool for neonates, and it seems like you guys are very dedicated to the neonatal population. But in theory, it sounds like the worst population for this project because of they breathe erratically. They have apnea, and and their their diaphragm is obviously very small. God knows if you're picking up the right electrical activity. So when when the neonate presented itself to you guys in your research and in your in your trials of of Nava ventilation. How did it go? Did you guys say, oh, boy, this is a terrible patient population.


Dr. Jennifer Beck 18:43

Yeah. So yeah, you're correct. The adult population has a very regular breathing pattern that you can predict. And the adults actually it's interesting because they use a lot of sedation. So often, we would go and in the early days, we were trialing just even just the neural trigger. We would put the catheter down and the patients would be snowed and you'd have no signal. We're like, Oh, it doesn't work. Right. So. So one good thing about the babies is very rarely they're sedated. And most of the time they have, I would say good spontaneous breathing. If they don't, it's something to question and ask why not. So we were surprised. So we applied to do NABBA extabit, the baby and the nib Naveh using a servo 300 prototype, I think this was, I don't know, 2003 or something. And so we got health approval. But the research ethics board said we're not letting you know ahead. We want to know what the signal looks like in these small babies because we'd only done pediatric studies in Montreal. We didn't really have premature babies, you know, like 1500 grams or less. So they said we'd like you to do repeated measurements and babies over several days for one hour at a time. And that's when we discovered the hives. The ability of the breathing patterns so that we were able to characterize it, and we could see, you know, phasic breathing just like an adult, but then the signal wouldn't go back down to baseline stayed elevated. And then we would have these huge neural inspiratory efforts, which we now know, we're probably size and recruitment. And then, as you mentioned, the central app, and it was the, you know, we could spend hours and hours trying to figure out the pattern like, Okay, do the size come up for the apnea? Or do you know what, what happens and all that. So, it, the neonatal breathing pattern certainly pushes Nevah to its limits, but we have all the protective features there. So for the apnea, we have a backup. And we have a bill for McCain now has put in different apnea times that you can set and depending on the principal and the way that your unit works, some people put that at the time very low, which means if you have no Adi for two seconds, then it would kick into backup. But the philosophy of that unit is well, at least I know that 50% of the time, when my baby is reading, they're synchronized. And when they're not, they'll have the backup. And then there are those people who think that the baby should wait five seconds, or even 10 seconds, before they resumed their their breathing patterns. So and then you have your pressure limits for those that are going to do the repeated size. So if the size come in too often, there'll be pressure limited and hopefully avoid any kind of injury to the lungs. So yes, that also they have these very strong vagal reflex, which adults don't have. So the very first senior person I presented NASA to said to me, Well, Jennifer, if I just blow in the face of this baby, he's going to do a big sign. So there, it definitely pushes the limits of the mode and was makes it challenging, but at the same time, I'm really happy that since the very beginning, when this was introduced, at first, there was some critique about oh, this is like being a drunk driver out there driving a car, you know, those kinds of things. I'm really happy now that all the studies that have come out to show that this is feasible, all the way down to I don't know, six 500 gram, babies 25 weekers, and that their reflexes are in place and are able to control this more or less safely. And most babies, there are some papers that have just come out recently, looking at 1000s and 1000s of breaths of babies on NABBA. invasive and non invasive I think it's Dr. Signs group where he published what are the typical pressures and volumes you get in babies when they're ventilated. And they're all reasonable, you know, they're anywhere from four to six mL per kilo. And the pressures are within limits. reasonable limits. So it's, it's reassuring to us and you'd asked me 10 years ago, what a normal EDI was Christopher was talking about a range of five to 15, I wouldn't be comfortable back then saying but now uncomfortable and agreeing with him that it is somewhere between five and 15. I guess you have something you want to but


Dr. Sinderby 23:06

I think also think that clinically like that has become like the little bit of a problem because the somehow the I don't know if it comes from respiratory therapy school or somewhere but people like oscilloscopes. So they want to see that in one breath, the synchrony of the one breath, they synchrony of everything is like it. And if you take pneumatically, trigger mode, flow, pressure, volume, whatever you want to trigger on and you're happy, usually, you can forget about synchrony they will never be think there was the machine will live its own life and the baby lived its own life. And they have nothing in common except that the machine is blowing air into space once once in a while. And I think that when you take the neural signal, that's that's the fantastic thing about having that feedback is that if you extend your time on your screen to the longest actual time in real, like the real time screen that you have a VDI and make it as long as possible, that's when you can start to see the written that the baby is breathed with because there comes a period of slow steady state breathing, then they wake up and then you can see that when they start to move that you get nervous, like the signal becomes a little bit erratic. And then 123 You get the sigh So a an apnea. And once the apnea ends, usually it's followed by a long recruitment period or OSI. And these ones you don't see if you look at three seconds of the signal. You can never see this if you look at half a minute. You get like something like 30 breaths on your screen you now you can actually see what the baby is doing. Yeah. And that's because the synchrony is I can see the synchrony you can't do shit about anyway because this thing


Dr. Jennifer Beck 24:49

allows us where


Dr. Sinderby 24:54

the synchrony is what I mean. So let's say today that the best synchrony you get in the neonate with neural control, then the only thing you can do is accept it because you can change it, the trigger is fixed more or less, and the set off and the cycling off is fixed. So I mean, if you would have an artifact that would do like say that there is an ECG replacement that makes a breath not trigger, well, then you get the breath without the cyst. If there would be something that leaks through that would make it tricky. But then you would get the same thing as you get within IPPV, whatever I mean, it's, you get an A synchronous breath. But these breaths only occur with a very rare in within long intermittency, whereas otherwise, it's all the time. Yeah. So I think the point is that one should stretch the screen, look at the breathing patterns, because that's how the brain responds like over time,


Ben 25:47

so So let me ask you this because I want to I want to be devil's advocate a little bit and every time I've had this argument with about Nava, where I feel like I'm an advocate of the the most common argument I hear against it, especially when we're talking about the small babies in the NICU is often our this catheter just sits somewhere in the esophagus and there's tons of electrical activity you could pick up from, you're not really 100% sure what you're picking up. And that's something again, I have heard multiple times, and and we're so happy to have you on so that you could we could hear it from you. And as to what is the what is the answer to that to that criticism?


Dr. Sinderby 26:23

What is the same thing I would say that the vaccines we have today for COVID doesn't work, it's like this, it's the same thing. Okay. I mean, it really is kind of like, I mean, we have a detector that is detecting ECG signals. So anything that comes from the heart, we will pick up that. And usually we replace it so that it will be like that we give like a little bit of a previous signal is going to be continuing. And that is going to fade out to less than less increase. And you can see that on the screen if you look really carefully. And when it comes to the other electric electrical activity you can get which is the esophagus, that comes as bursts. For it still lower esophageal sphincter, those signals are typically somewhere in the 510 Hertz range. We don't let through a single signal that is less than 60 hertz, or 70 years. So those things don't exist, they are filtered out. So that's like the end when you go to 60 hertz, we have filters for 36. Is it 60 Hertz in North America or 60s? So in North America 3061 80. Also on every frequency, there is a filter that cuts out that signal. So all electricity you have, if you have an electrical system that stays at 59 to 61 hertz, there's nothing coming training it can you so so I don't I don't think that that


Dr. Jennifer Beck 27:51

the I'd like to give a bigger picture answer to your thing about people who are in doubt of the quality of the signal. So when Krista and I first met her, we can tell you some funny stories about that time as well. But so my PhD thesis is all about how the catheter should be designed and how to take out the signals from there. And so I have eight papers in my thesis, so we have a very thorough scientific evaluation of the EDI signal in itself. And that was complemented by a lot of work that Christopher was doing at the same time on things like crosstalk which is probably what your colleague was asking you, where you have EMG or electrical signals from other muscles, and how to get rid of them, including the heartbeats which he just mentioned. So we have maybe six or eight or even 10 scientific papers with mathematical modeling. Because we always start with a mathematical model then we go into the experimental situation which is non human, and then we go to humans and we usually tested it in ourselves healthy people first. So that's one of the funny stories is Christer trying to put down one of these catheters and throwing up on my shoes and me falling in love with at the point is is that this is actually the we would never have been able to sell the technology without proving first that this is a a reliable and physiologically representative signal. So crosstalk from other muscles crosstalk from the ECG the positioning is based on a cross correlation algorithm. So we are directly perpendicular to the diaphragm, our array of electrodes so we know that would have above and below has to behave a certain way mathematically. And we were able to reproduce that in the animals of the experimental lab and and in human subjects. And in fact, the first time we ever had to do a demonstration, I remember one of the corporate people said to my technician who volunteer to put down the catheter, could you please jump up and down? And so my technician will have the catheter down and was jumping up and down.


Dr. Sinderby 29:56

The gas just stood on his head? Yeah, could


Dr. Jennifer Beck 29:57

you please do a dance? Could you please string some orange Seems like we were really, really doing everything to show what can or cannot affect the same thing.


Dr. Sinderby 30:06

I think a very important thing to to this is to say that the I mean, there is only 110, there's only one periodical signal that exists. That is not the heart. And that is breathing. Correct. And that's the and then I think the only shortcoming we have today with now if it's still there, I don't know. But it was something that if the heart rate coincides with the respiratory rate, we are kind of blocking out the use of NAB, I think. But in general, I mean, you have in the in any data set that you look upon, you can see the heart rate, on the Ross tracing, as it goes, boom, boom, boom, boom, boom. And then you can see the breeding like and I suggested many years ago, they should actually put the speaker so that you could hear the electrical activity, because it has such a different frequency compared to the heart. So you would hear the boom from the heart, and you would hear the kind of like more fussy sound from the high frequency activity of the die. Interesting. So, so there is all this, but in general, I will say for clinician, I mean, I say, if you follow the thing that you see that you have a heart that is in the vicinity of the center of the catheter, the electrode array, I don't think you have any problem. I mean, you can push it too far in you can land against the abdominal wall, and then you would get the reversed part, then you would get expiratory muscle activity. And we have problems with that in the beginning. And that was that We therefore recommend that and I think it's still this in the in the thing that if you're worried about the signals you do in the pollution, that you actually see that the actual activity or you take away the assist. So you see that when you actually see that there seems to be an inspiration that air goes in that you're in that case, or actually seeing that the signal occurs. That's inspiratory. Yeah. And it could also be at the upper airways. But the thing is, if you want to put it there, you have to either product like five centimeters, so three centimeters, or four centimeters too far in, or the same house, and over a total distance of 16 of 16 centimeters. So 13 centimeters, I mean, that the error is so big that if you clinically would do that, how would I ever let you put the effort?


Daphna 32:28

Yeah, well, that's what I think by spending time at the bedside and looking at the patterns, especially with Nava. I feel like I learned so much about the behavior of babies, right? And it makes sense why giving the same breath every time is less effective, potentially in a baby who does who is breathing spontaneously, because it is going to change over the time it changes with sleep changes with handling changes with apnea, you know, and how do they recover. And so it makes sense, especially if you're able to take time at the bedside and look at the you know, signals, and a lot about the weak cycling and the respiratory cycling of baby. So I mean, I feel like I've learned more by using Nava, to help me understand how babies are responding to stimuli in the unit. And for somebody like me who's really interested in neuro development, it helps me understand a lot about what's going on. And like you said in the brain by just watching their behavior through breathing, which I think is cool. And, and so while it was very hard for you guys to study initially, I think Navah is a good technology for babies because they're changing, so So randomly.


Dr. Jennifer Beck 33:52

And I think the whole comfort issue has been not emphasized enough, because it's been more of observation by parents, for example. I know there's a group in Finland, I have a very good friend there who uses a lot of nav and she said to me, they have family centered care. And the parents are all like making coffee in the family kitchen. And oh, how come your baby's so comfortable? Do they give her some drugs? No, no, she's another oh, what's not my you know, so they're all starting to talk about it. And I wish that somebody would come up with a good study on comfort. And I know like, we talked about all these things like cortisol measurements and mid cap and all these kinds of video things from all angles of the room and all those but I don't know if a patient parent satisfaction, kind of a comfort evaluation, I think would be convincing, at least important study to do. Yeah,


Dr. Sinderby 34:53

but I think that if you look upon conflict, I mean, it's it's what is not affecting your breathing pattern. Is anything I mean, you can have, you can scare somebody you can, you can do whatever, their breathing pattern will always be effected. There's just a baby's breathing pattern or not as trained as ours, they are, and they are also having a lot of reflexes that we don't have. So if you, if you push a flow there too much, I mean, then you get the heads paradoxical reflex, so that then they start to gasp, if you give them too much, then they stop breathing, because then they have to have a hearing reflex, if you take away the, the the teeth, then they start to pull inwards because they need to recruit themselves. And that's also here, employer, and so on. And I mean, in between there is like they have in the actual breathing pattern. They're tweaking their inspiratory time. So they're experts over time and, and their recruitment patterns and their activity all the time to try to satisfy the breathing. And I think that we could usually see in babies that are happy and satisfied like it, especially if they sleep or whatever. But babies dream a lot too, I think so that there's a lot of things that affects them. So if they have follow dreams, even if they haven't seen the movie yet, but it would, it would definitely affect them too. So So I really think that it's the the pattern generator that is important. And I think that that's, that's when you should look on the on the bigger picture. There's the A synchrony, like how many milliseconds it goes from that you start your neural like inspiration till the ventilator triggers, that is not so much the issue. The issue is much more how do you actually behave in this situation? And


Ben 36:45

I think I think this is this is where I wanted to I wanted, I think this is this is exactly what I think this is the essence of what we're talking about. Because I don't know, if if if there's, I don't know if I agree that we we can we don't we cannot learn anything from from other modes of ventilation wholesale. But I do think that Nava has highlighted something that we've learned from other monitoring systems like the hero monitor, which is that constants and and lack of variability is normal. I think this is where chaos theory and other and other fields have shown us that know this variability, a breeding cycle should not be identical, one after the other, it changes all the time. And when you think about how we set those settings on conventional ventilators saying, well, your volume is going to be the same every single breath. That makes no sense.


Dr. Sinderby 37:34

Well, it means that you could be heavily sedated, which is usually the case in the adult patients, as adults.


Ben 37:40

And I think and I think we're never really introduces something that is very modern, in my opinion, is this idea that every breath is different. And, and the and the machine will will will constantly adjust and because we're on battery and under electricity. So I think this is this is to me where where it is, on one hand, very modern, and also very philosophically interesting to say every breath is different, and the machine will work with the baby. Like Daphna was saying earlier, quoting you guys this personalized ventilation of yeah, maybe you won't, maybe you'll have a bit more frequent type of work of breathing, but maybe maybe you want and that's still okay. Anyway.


Daphna 38:15

Well, exactly what you're alluding to is actually by my next question, and I realize we're already getting to be short on time. But you know, what, this was really a revolutionary kind of technology, exactly. Like you're saying, and your ideas are well taken, but they're, they have met resistance, I'm sure because of doing things in medicine, the way we've always done things in medicine. So, you know, what's your recommendation for people who are really trying to, you know, shake up the industry? And, you know, how do you get through to people, when you know, something, when you you know, you have this vision? And and it's not the way we've always done things? Are you gonna?


Dr. Sinderby 39:00

I think I have a short answer to that question. And I think that what you're seeing trends today,


Dr. Jennifer Beck 39:05

it's been for 30 years, that's fine. But


Dr. Sinderby 39:09

there has been in the recent years, the only way that clinical people have been able to force industry into something is for example, you can see today people are starting to use this video of catheters, esophageal pressure casters, so in adults they measure esophageal pressure in order to measure the work of breathing is the one that usually what you see if you're lucky is the esophageal pressure that is related to breathing. But if you have a patient with a COPD or enlarged heart or whatever, you usually see the cardiac waveforms, like when the heart is beating, and that's beating on the balloon. But what they have done, which I think is right way to go is that they have gone together in groups that are groups that are actually interested in the same field. So they are interested in the use of for example, this offer To catheter or nasal prongs or whatever, anything, but they have clustered and created groups published papers as groups. So they call the view you would call them to yourself, they're the EDI or the Nava Nava response, whatever group is, but a lot of physicians that have gone together in many countries because today the world is flat, so I mean, you can do it worldwide. But get people's work on and go out and say if we're going to put the tender, we are going to recommend or buyers here that we have to have at least this many sets this much of Catherine like ventilators that can measure die from activity. Because that's what happened with the esophageal pressure. Like 10 years ago, there was a company 50 started to go in to do esophageal pressure measurements. And I asked the salesperson that the guy who was in the company here in Canada, after three years on the market, how many Catholics did yourself CRO, then this plug group came about. And they started to say we want to see as a fudgier pressures. And they put it in tenders that the ventilator have to have a sufferer do pressure measurements, otherwise, we will not buy the ventilator. And 123 Now people started to put esophageal sensors, pressure sensors on their ventilators because they were afraid that you would not pick up. So if you would say for my neonate, baby, I want to see an EDI catheter. And in that case, I mean, it's it's a business thing. So the companies can fight between each other, how they get the license on something or how they do whatever or if it's not even, whatever if it's public domain or so on. But whatever they do, it creates a market but the pressure must come from you guys. Like you who you have the powers to do with if you get together, but you have to do it in many countries and many people, and it has to show on the tender so that whatever is sent to the company to say this is what we want on our machine


Dr. Jennifer Beck 42:04

can make it look like a neat. Yeah, so that's,


Dr. Sinderby 42:08

that is definitely a I would say that the the fastest and easiest way, if you want to make a change, because I can do it. I thought I'd done everything. Awesome.


Daphna 42:22

Well, that's really I mean, that's really inspiring that you think, different answer completely. That you think clinicians can, can influence the market. But Jennifer, Dr. Beck, I'd love to hear your response, then it's a different one.


Dr. Jennifer Beck 42:36

I thought I'd maybe I misunderstood your question. You were asking how can I convince people that this is important? And I I've always been kind of encouraging the slogan tense is my patient breathing? You know, to ask that question at the bedside? And then I have a little flowchart, of course. But if the answer is yes, then well, are they breathing in synch with the ventilator? And if they're not, well, how do I fix this? And if they are, that's great, because then you can trust your respiratory rate measurement. So it's a lot easier to convince people in the adults about the is your patient breathing question, because they're so heavily sedated? And usually they're in control mode? And but with the babies? I don't know, like, I think just asking at the bedside, is my patient breathing? Is my patient breathing hard? Is my patient breathing in sync with the ventilator? Those are good questions that nobody can really answer that's that's you had the EDI signal?


Dr. Sinderby 43:36

That's the question that that is related to a clinician. So that's, that's that's what the clinician should take from like the why would the clinician be interested in ABA or in dying from activity? That's, that's, that's one question. But if a clinician as you guys, if you like it, and you want to see more of it, the only way that you can affect it is that you would have to say to your purchasing people that this is what we want on our machine, because this is what helps us. Now if this is like a single company doing it, well, then if they say that we we we actually will start to recommend this. Well, then it's about the law of public purchasing. But I would swear to god that in that case, there will be other companies coming out doing the technology to when they will be the same thing as with ECG that, you know, patents go out the democratisation. There is there will be there will be competition. I mean, it's it's it's but it can only be competition if you guys want it. I mean, that's the problem with the adult market is that the adult business is that when you have problems with the patients, so called a synchrony problem, what do you do? You sedate them. You turn them off and put the remote so when you guys can't do that, you have to actually make the machine go with the patient so you have to go the other way. If you can convince like, people to understand that, but there is also another issue to this and I think you'll be asked me to how many people below 50 years of age, so 45 years of age, have you seen using Java?


Ben 45:14

Well, I was gonna say zero, but my sample size is terrible.


Dr. Sinderby 45:20

You say, no, but if you if you look upon the market that we have grown up with, is that we were young when we started this, but the people who were in the market were old. And the problem is that many times is that they will people mean the users are the patient, the users, the users. And this kind of like the users that had like a, what you call like an impact when they go out and give lectures. So we have like, 10 years, 2015 years ago, I was out there talking about things about the synchrony, and so on, a lot of that is being repeated still today. And I don't understand why because we are looking for a synchronous and everything. And I mean, when you can see a synchrony, even the blind can see it, if you have a catheter down, like an EDI catheter, whether this patient is adult or, or whatever, then why do you worry about something where the problem is actually solved? I mean, the thing is, how do we go forward, but in this case, I think that there is a lot of these generations shifts that people who has been kind of like, hooked on something and are stuck there, when they come to a power situation, they will let go. And I mean, this the same thing with me. I mean, I defend like the the AI and everything like that, and so on, and but I don't try to get into anything else really, either. So I think for clinicians, I mean, it's, it's, it's very easy to have that thing that I mean, I've done this for 35 years, you know, and when I see that they do like this, that's what we do. It's funny,


Ben 46:57

what's funny to me and not and to a lot of other people is this idea of resistance, and retention of of a dogma that's not really rooted in evidence, I've had a lot of interest in looking back at some of the things that are very dogmatic, especially in neonatology about what is the tidal volume of a baby and you start digging? And you're like, hold on, where's that data? And you realize that we're really on thin ice when it comes to what we've accepted as very much the norm. And I think this is to me, my my ability, in my opinion, to look out for new technology and new things has come from the fact that I've dug into what we're doing to see where's really the evidence, and a lot of times you look and there's and there's nothing and you say, Well, you know, if well, there's no reason to, to hold on to, too unfounded, some, some some of the practices that sometimes are not really rooted in evidence. So


Daphna 47:50

that's training needs to say, so why are we doing it that way?


Dr. Sinderby 47:57

On rounds, this is like where we are heading these days. It's like, I mean, we are kind of like, parts of the mode thing, but, but a lot of it is that we are mixing the two parts of co2 removal, or co2 drive versus the actual loads on the respiratory system, or from the respiratory system. So if you have weak muscles, or if you have a high load, or if at worst, you have both you have weak muscles and the high load. And now you can get rid of the co2. So the thing though, is that the co2 drives you crazy. So even if I try to help you, you still want to read more. So when should I stop giving you me with more assist? Because in the end, you will be like if you were hanging from the Golden Gate Bridge in your fingers. I mean, what would you let go? No. I mean, you wouldn't stop before I really left you so that you know that you're really safe for them. But in some people that come in distress will be so big like that they we see it in adults a lot that you can bring up the assist. And the drive doesn't go down to bring up the assist to get the drive doesn't go down. So what happens? Well, the pressures of what's going up and the volumes are going to hysterical volumes. But when you don't have a volume in the baby, that would be this is as I'm saying with Nava, there is another thing that if you don't see that if you're increased your Drive like your Nava level enough, like so when you come up to levels of too much pressure starts to get really high. You should have seen a reduction in Drive. And that's like number one. But the thing what we're dealing with today is that now we started also to take away the co2 at the same time so that we can blow off co2. We haven't come come down to neonates yet but in adults and delta three killer which works nicely. And that is like we can blow off the co2 out of the trachea by having another tube in the tube. So if you ever heard about tracheal gas insufflation Shall we synchronize, we synchronize that technology that's interest so that it only works on expiration. So that you can actually now you can control both the two in the laboratory, we can control both the respiratory drive from a co2 reception level amazing and, and unload the muscles at the same time. Which brings us to the place that now you are close to doing everything you can in order to protect or prevent injury to a lung, like that's the and I think that that's where high flow nasal cannula has come to with it, that when you have babies that needs a lot of assists, might try to get more leads, so that you get more of a kind of the co2 wash out. Because you will flush the airways from co2 When you start to blow, kind of like with the big league with a building. So so it's it's another interesting area, in fact that I think, close to retire that seems like you know, we are not we know this is this is something we've done for over 10 years. So this is not the New


Dr. Jennifer Beck 51:07

Deal, we do have an interesting project going on right now with the negative pressure ventilation with them. A little new vest, we call it which is kind of like an old CQRS. So it's just sits below that sits around the abdomen and it's sealed. And you can do synchronized negative pressure ventilation. And so instead of having a continuous negative pressure like they used to in the olden days, and they sealed up next, we're just doing a gentle unloading of the diaphragm, intermittently using the continuous Nava technology custom position before which is without the triggers. So it's just very, very gentle unloading of the diaphragm synchronize with the baby's breathe,


Dr. Sinderby 51:45

it technically expands the abdomen from the outside, you're feeling a vacuum. The diaphragm is weightless. Below it there is weight to the diaphragm on the upside, but not on the downside. It's interesting.


Dr. Jennifer Beck 51:58

And then you can combine that with any kind of positive you're doing whether it's invasive or non invasive. And I gave a talk in Poland last week. And they were saying to me about this abdominal and let me be well, what about the skin? And did it only been on for long, and I said doesn't matter because if you have the catheter down, you can interchange your interfaces, right? So even if you are doing non invasive NABBA and you you're putting your prongs in and you start to see damage, well, then maybe you could switch to the neovascular maybe switch to a face mask or maybe switch to a helmet. But you always have the EDI catheter down, you always have your neural signal that will control the delivery of the ASCEND.


Ben 52:33

You could synchronize and you could synchronize both.


Dr. Jennifer Beck 52:37

Yeah, so that's that's what we're kind of working on.


Ben 52:40

We wanted to ask you about some personal questions. Obviously, we're over time but that's okay. I'm enjoying this discussion very much. The what is it? Like? What is it like to work on? I guess a project that is very, very large, it's it's competitive, it's difficult and your husband and wife combination is that make things easy? Difficult. I'm wondering. Wondering, I'm just wondering, I think to me the biggest hurdle to being husband and wife working on these types of project is I'm assuming the work never stops. I mean, because if you're always in discussion, there's not going to be that point in time where you get home and you have to pause everything you can always continue on


Dr. Jennifer Beck 53:19

now know our grown up, our grown up children know what Napa is and have been at the booth many times and traveled with us when we were doing the circuit let's call it but first your Krister has not really ever had a vacation and for as long as I known him and his best creative times are when he has jetlag. So if we try to get to Europe or back I will look over and I will see somebody staring at the ceiling and I'll say what and then he'll tell me his idea so I have to have a notepad on my nightstand.


Dr. Sinderby 53:53

Sir I don't know I think the when you're talking about the husband and wife thing you have like if you have your if you have a good relationship, I mean that's number one. You must have that and you have to have like if you're like me, you have to have a very you say like a wife that puts up with a lot but I think generally what's the important thing is that our work style is not like we've never we never go to work. But we never go home from work either. We are always but it doesn't matter like so we were in Paris like two weeks ago and work there all the time. We were in Sweden four weeks ago and worked there all the time. We're going to Florida next month and we're going to work there all the time to be worked on our walk and every kind of walk we go for like it's a business brainstorm. It definitely is that to get like, you can say we have been working with with it was first period and then it and then we work with Siemens and then with the ATA with my K and I mean, we've been working with these companies since the, I don't know, they will say mid 90s. And we've always been minimum 1015 years ahead of their research departments. And therefore research guys don't have time to, to kind of sit down as we can go like day after day, week after week, month after month, the same idea into the lab tested, see what happens. But out again, try new change your thoughts, whatever,


Ben 55:30

you're much more agile than they are.


Dr. Sinderby 55:34

They Yeah,


Dr. Jennifer Beck 55:35

we also have a great team. Like we have Christopher's old mentor, who was a mathematician, we have a great programmer who can Krister gets an idea on a Sunday night about how to change a cycling off criteria with Nava. And we're using a prototype in the experimental lab, the guy will program it, and we'll have it Monday morning. And we can actually test the concept. And we have a great, great technician who has been with us for 30 years who are trained in programming and analysis. And he is also one of those guys that you say, I wonder what this would happen today. And, and he will do like an offline simulation of using data to prove him wrong or right. So we have a really, we have a good team. That's


Dr. Sinderby 56:14

so the thing is, we don't put it like this way if you take basic science, but in clinics. So I mean, we do basic science on ventilators, if you put it that way. So instead of looking for how to solve the problem with the COVID virus, we try to solve the problems but not by comparing one machine to the other. That's like not what we do. I mean we we develop new technologies for new ideas and new and it's amazing like the you think that that you you reach the end and then you think about it again and 123 You have a new idea and fine on the test it and


Ben 56:49

it's working spoken to you for an hour, I have a lot of respect for the for the researchers working with you trying to prove you wrong.


Dr. Jennifer Beck 56:58

Well, my favorite, my favorite. My favorite experiences is when we were developing the EDI catheter, I came home I guess I went to do groceries with the baby. She's now 23. But and I look over in our backyard, and there's Krister with wires and tubes and, you know, pliers and whatever. And he's building the catheter, that it's the way he wants it to be built, you know,


Dr. Sinderby 57:22

for testing. And that's actually the catheter that's received, when you see today is that final version that he did, is done in the backyard in my


Dr. Jennifer Beck 57:29

backyard. So interesting. Well,


Dr. Sinderby 57:33

it took a lot more than that.


Daphna 57:35

It's a good reminder for us, clinical people, right that the scientists behind all the technology are just having the same struggles with work life balance that that we do. See.


Ben 57:49

And also that sometimes I feel for us clinicians, we feel very frustrated, sometimes hitting our head against the wall of the institutions of the hospital, we feel like ah, this is like this monstrosity. And I know I hear some frustration sometimes in what you're saying. But I do feel like you're an example of how to break through with persistence and passion because clearly because I know you're working on more newer things and but at the end of the day, Nava is at our bedside down here in Florida, we are using it and it works well. And I think this is a testament to to your work and your perseverance. So I think this is a message for all the trainees and all the people out there who are committed to innovation.


Daphna 58:29

And we're not being we're not being paid to say this. We really like the technology. So we really appreciate your well all of the work that you have done, but specifically your time today.


Dr. Jennifer Beck 58:40

Well, thank you very much for inviting us that was very was fun. Very nice.


Ben 58:45

Is it okay for us to share your email address in our show notes in case somebody has questions or wants to collaborate with you guys in on the project.


Dr. Jennifer Beck 58:54

And I can send you we wrote a review that just got published summarizing all the work for the last I don't know since 2007. So I can I can send that to you. You can put it up because I saw the other guests had posted a lot of their articles.


Dr. Sinderby 59:07

I think that's as you say, like like a testament or whatever to that, that. If you see that it works then then why not use it? I think the like one of the pediatrician Petter Ravensburger in Switzerland. I asked him like, I think first year that he had gotten about 97 to 2007. Sorry. And I said to Peter, you'd been using that but yeah, so what's your impression with it? You know, what's good about it? Babies fall asleep?


Ben 59:39

Yeah, yeah, that's right.


Dr. Sinderby 59:41

And that was the trick babies. Yeah. Anyway,


Ben 59:45

thank you guys. Thank you guys so very much. It was great and we'd be looking out to for for new stuff coming out of your life and thank you for listening. Listen to this week's episode of the incubator. If you liked this episode, please leave us a review on Apple podcast or the Apple podcast website. You can find other episodes of the show on Apple podcasts, Spotify, Google podcasts, or the podcast app of your choice. We would love to hear from you. So feel free to send us questions, comments or suggestions to our email address NICU podcast@gmail.com. You can also message the show on Instagram or Twitter at NICU podcast. Personally, I am on Twitter at Dr. Nikhil spelled Dr. NICU. And Daphna is at Dr. Dafna MD. Thanks again for listening and see you next time. This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns, please see your primary care practitioner. Thank you

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