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#021 - 📑 Journal Club 11


NICU journal club the incubator podcast

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


Qualitative indications for tracheostomy and chronic mechanical ventilation in patients with severe bronchopulmonary dysplasia. https://www.nature.com/articles/s41372-021-01165-9


Association between Term Equivalent Brain MRI and 2 Year Outcomes in Extremely Preterm Infants: A Report from the PENUT Trial Cohort. https://jpeds.com/retrieve/pii/S0022347621008258


Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783715


Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001241.pub8


Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial. https://www.nature.com/articles/s41372-021-01018-5.


Adverse Events and Associated Factors During Intra-hospital Transport of Newborn Infants. https://www.jpeds.com/article/S0022-3476(21)00859-3/fulltext


Digital tracheal intubation and finger palpation to confirm endotracheal tube tip position in neonates: A systematic review and meta‐analysis. https://onlinelibrary.wiley.com/doi/10.1002/ppul.25551


The DELUX study: development of lung volumes during extubation of preterm infants. https://www.nature.com/articles/s41390-021-01699-w



 

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


SUMMARY KEYWORDS

babies, infants, looked, study, tracheostomy, paper, transport, trials, author, adverse events, outcomes, patients, interesting, question, gestational age, meta analysis, bpd, twitter, people, group

SPEAKERS

Daphna, Ben


Ben 00:04

Hello, everybody, welcome back to the podcast Daphna. How's it going?


Daphna 00:52

I'm good. I'm excited about some of the articles we have. I feel like they are relevant to what's going on in our in our unit. So


Ben 01:01

glorious day for journal club.


Daphna 01:05

It's always a glorious day.


Ben 01:07

I don't know about that.


Daphna 01:10

Well, how are you doing?


Ben 01:11

I'm doing good. I just got back from California, went on a family trip spoke at a fellows conference. And that was really exciting to see a lot of fellows presenting their research, being passionate about research and, and about their future sort of professional endeavors. So it was a lot of fun to interact and meet a lot of these prospective colleagues. There are there are colleagues already, I don't know why I'm seeing prospective but like prospective attending colleagues. So that was a lot of fun. California is really nice. Yes, stating the obvious way. Yeah. We, I guess we should start off the podcast by thinking again, Dr. Jensen from being on the show. It's the episode is extremely popular. And I really appreciate it when people of his caliber come on the show. And I just can't I mean, obviously, we had so many other people before that come with such humility, you know, and tell you about sort of their struggles, what worked, what hasn't worked, and not really trying to sell a overly positive narrative that sometimes, you know, this forced positivity that sometimes we feel like we can't really contend with. I think it's nice to hear that it's a struggle for everybody.


Daphna 02:23

Well, and I think that's what we that's what's been so fun for us. Doing this is just getting a talk to people in here about their lives, you know, you know about their research, but to just to hear about their lives and how that fits in with their careers is is neat, right?


Ben 02:39

I guess the other thing that we'll do Twitter feedback at the end, but we wanted to thank everybody on Twitter, because we crossed the significant milestone of 1000 followers on Twitter's on Twitter. And we're very thankful. I mean, I always see this as a humbling milestone where where we have a lot of responsibility to the community, it means that we're doing a good job, but we have to keep doing it diligently, rigorously and frequently. So thank you, thank you.


Daphna 03:08

Yeah, and people, you know, keep engaging with us on messages and tweets, it's, you know, it really kind of fires us up. And we're finding ways to collaborate with people, which is super cool. And then just really seeing kind of the Neo Twittersphere like really growing in so much. I mean, not just what we do, but there's so much information being you know, disseminated that I think is like totally relevant to practice. So it's cool.


Ben 03:36

Yeah, I think Dr. Narvaez goal of growing your Twitter is happening, doing it in front of our eyes. It's he's doing it. That's awesome. Okay, let's get you a journal club, then. Tell us where you want to begin.


Daphna 03:49

Well, I know that you have been trying to get to this paper regarding tracheostomy


Ben 03:54

fine. So there's a few BPD papers on par with. I like to look at these papers, especially when they're published in the past few weeks. And they tie in very nicely with the guests that we've had on and so on and so forth. So this this paper was published in the Journal of parasitology. It's called qualitative indications for tracheostomy and chronic mechanical ventilation in patients with severe bronchopulmonary dysplasia, the first author, I'm going to butcher that name, I'm so sorry, Sushmita Yalla. Prada, I think is the name. And this is part of a larger group. That's composing the Children's Hospital neonatal Consortium for severe bronchopulmonary dysplasia subgroup. So yeah, a long list of authors. So I think this paper is interesting, right? Because the objective is to describe potential indication to pursue tracheostomy and chronic mechanical ventilation as a as a byproduct in infants with severe BPD. I think this is a question that is an extremely relevant one. We don't really know the answer. Everybody's have to sing rather differently. And and so this this paper really tried to get a sense of as to what is motivating people to pursue a tracheostomy, something that Dr. Jensen really spoke about last week, where he said, we're not really sure what we're doing, we're just tinkering with the patients. So it's nice to see at least an attempt like this at trying to get a consensus sorted out. So the objective of the paper was to identify provider defined indication, prompting the decision to pursue tracheostomy and infants with severe BPD. Within that neonatal consortium, so they had a group of 34 participating hospitals. And they basically sent out surveys, the surveys were organized in four sections, there was about 100 questions. And what was very interesting is that they did leave, in the final sections of the survey, open ended question where people could really write in and sort of not really be constrained to a format of multiple choice answers. The interesting thing as well was that they did not force the centers to answer every question, you could submit a partially filled out survey. And so and they gave, I think, people about nine months to get around to filling the surveys, and that happened in 2018. So out of the 34 sites, they had 91% response. So that was 31 sites. And I think interestingly enough, 13 of the center's had a self identified BPD programming. They were also asking institutions if they had a consensus within their own institution, right? I mean, this paper is trying to provide a consensus to the approach of when, when and how should we treat patients with severe BPD. So it's interesting to see if each individual center had a consensus themselves and four centers. So that's 13%, reported that they had such a criteria and 87% did not let's get to the to the important part of the results. So among the responders the most common criteria that contributed to the decision for tracheostomy included the following airway and ventilation subcategorized as airway Malaysia, need for higher peep endotracheal, positive pressure, failure to thrive on non invasive support, multiple courses of corticosteroid therapy, pulmonary hypertension, and poor growth and feeding. The least common indication for tracheostomy included postmenstrual age, so their age was not becoming a predominant factor in their decision, social considerations, which I think something we could argue, and an interesting one, which was tolerance, slash avoidance or thriving with developmental care 8%. And I wrote next to it, Daphna is going to be upset about that. But that's okay, we can talk about it. I could hear you scream when you read that that. Like, like we said, growth parameters contributed to the decision, but they were not given as high of a priority. And so linear growth was a factor in 41% had growth in 35% of cases. Interestingly, I'm going to finish off by this, the next one of the sections surveyed, specifically the parameters, right, I think this is what people want to hear about, like, what are the parameters when, when is the number that I could say, Okay, now you need a trick, which is obviously not the right way to look at it. But it's interesting to see if people did have parameters when it came to support and things like that. So among 29 responders, the most common range for P co2 was 76 to 85 millimeters of mercury and FIU to superior to 60% Peep of nine to 11, a respiratory rate 61 to 70 breaths per minute, that's obviously not intermittent, right? dimensioned, consistently postmenstrual age of 44 weeks or more, and a weight that is less than the 10th percentile at 44 weeks, they looked into qualitative analysis of the open ended questions. And they found that generally, providers were less likely to agree on offering tracheostomy if the infant was demonstrating weaning off respiratory support, or was on non invasive ventilation. I think that's a very interesting point. Because you wonder, is this a is this a mirage, right? Is this a little bit of improvement that we're interpreting as significant when really there is not significant? So I think this is something we should discuss. Anyway, very interesting paper. The conclusion of it is that understanding the range of mutation utilized by high level NICUs around the country to pursue a tracheostomy in an infant with severe BPD is one step towards standardizing consensus indications for tracheostomy in the future. The bottom line is this paper does not give you straight up indications to do it. They're not being validated in any way, but they're giving you a sense as to what other people are doing and it can tell you whether you're really far off from the norm or if you're within the pack. So I think from that standpoint, it's helpful


Daphna 10:00

But I do think it gives some sort of, you know, reassurance sometimes when we're when we're evaluating these babies, we feel like, what are we do? Like, is this the right choice? Or is it the wrong choice? And the truth is, is it's it's on a spectrum, right? So it may be the right choice for some families, the wrong choice for other families or depending on what the resources are. There's so many, there's so many factors, and we don't we haven't optimized it yet. We don't We haven't standardized it yet. So for those people who are you know, doing this in their units today trying to decide if a baby and we are we are we have a baby just like this in our unit. And I'm not sure we've reached consensus on our patient yet. You've, I know what you want to do for the patient, but I'm not sure we've reached consensus.


Ben 10:53

It's interesting, right? Is is whether as a as a group, right, me, I feel like the patient, those physicians who are involved in deciding for tracheostomy and a baby are usually pulmonary, leaning people. Sure. And then you wonder, Is my pulmonary bias, making me ignore other aspects of care like developmental tolerance, right to tolerate environmental care, or growth or social components? Right. And so I think this is where the next paper will talk about which talks about multidisciplinary care is very important, because it is a multifaceted decision. And the question that we haven't really answered is, number one, which factors should be weighed more or less? Right? What is the weight that we should be giving to certain factors and not others? And finally, who should be involved in making that decision? Right? How do you make it a team that is not too large, but large enough that you spend 360? Sort of the care for the patient? I think that's very interesting. Well,


Daphna 11:51

and I think that's why your point, exactly is why taking in some of those developmental considerations, and the nutrition and growth considerations are so important, because it doesn't, then it's not just about breathing, right? It's about all of those other things, because we can wean babies and make it look like they're being successful. But when those other things start to fall off, and then we we've proven that the baby's just not ready yet. And then then part of the decision really does become At what point do we keep babies hospitalized and sacrifice development versus getting them home with a with a safe airway, that is something we can teach parents to take care of. But is is a life changing event for the whole family. And not all of our families can can do the care and in the current climate, not all of our babies can get skilled nursing. So there's so many complicating factors. And I think a lot of it does depend on where you're at what your system looks like. So we've died digressed a little bit with their their findings were but I think some of these, you know, are you know, the baby still intubated and is very, very old. Well, some some babies are an easier decision than than others, right? And then then it's really about how much time? How much time do we give them to show to show that they're making progress?


Ben 13:25

And it made me wonder, are we ever going to get to an answer in terms of what is the proper the proper algorithm to use? And what is the trade off right between long term development versus the short term morbidity of having a tracheostomy, but these babies are so complex, I'm wondering how how we're going to ever manage to create a trial that would be large enough and, and well designed to actually answer that question. That's, that's yeah, somebody's listening and has good ideas.


Daphna 13:54

But I think it I think, to that point, it does take a kind of multidisciplinary approach.


Ben 14:02

Okay. Yeah. I mean, I think we said everything that needed to be said, and the most part most importantly, that you need, you need, you need a team. And don't because you're because you and I are uncomfortable with deciding when to take a patient, it doesn't mean that other people are knowing and all confident about when to do it. It's a big topic of discussion. Yeah, just keep an


Daphna 14:27

eye on it. I think that, like you said that opening statement was that this is really a frustrating time for families, where families start to lose trust in the system, because everybody they talked to has a different opinion. And so having a consensus as a group, whether or not that aligns, you know, nationally or worldwide is still of some value. Because it I think it changes the parent experience, and then being able to provide anticipatory guidance as you're rolling into the 36 weeks and the 40 weeks and in the 42 weeks, and so that they're not taken by surprise when, when the topic is is addressed, I think that has been so valuable for our patients for us to really start addressing the possibility of a surgical airway earlier in care, and and if the babies don't need it, and, you know, the parents are happy that their babies don't need a tracheostomy. And then the babies who do need it, the parents have had the time to emotionally process some of that. So,


Ben 15:37

all right, I need to keep moving. I know


Daphna 15:39

all right. Well, let I would like to talk about because we talked about this earlier, but um, this this pre proof article on brain MRIs. Alright, so this article is entitled association between term equivalent brain MRI, and two year outcomes in extremely preterm infants a report from the peanut trial Consortium. So the lead author is Dennis E. Mayock. And so their affiliations are Wake Forest, the University of Washington. But again, they are part of the peanut trial consortium. And just as a reminder, the peanut trial was a phase three randomized, placebo controlled, double blind trial to assess safety and efficacy of early high dose erythropoietin as a potential form of neuro protection in extremely preterm infants. And then they had a subset of enrolled subjects that were identified and underwent MRI brain imaging between kind of 36 and 37 weeks postmenstrual age as part of their study protocol. And then those babies were followed until two years to do developmental testing, using the Bailey. So they're their objectives are, do our brain MRI findings predict neurodevelopmental outcomes at two years? corrected age? So we've talked about this before? I think that's an important question. Sometimes you get these MRIs and you don't know how to appropriately given territory guidance for families. And so that's what they really tried to answer. So the nitty gritty of their babies, they had about 110 infants assigned to EBO and 110 Babies assigned to the placebo groups. And then again, of the group that got MRIs. They had 27% of MRI scans were rated as normal 60% having mild abnormalities 10%, having moderate abnormalities, and 2%, having severe abnormalities, and then they looked at differences within the scores. So we'll I'll talk about that. I think most importantly, from the initial trials of the brain abnormality scores did not differ between the treatment group and the in the placebo. So that was kind of the first primary outcome of the of the study. So then then they looked at their group of babies, infant birth weights, were significantly different by global brain abnormality category, which I think is important. So the, the, the babies with higher birth weights, were more likely to have normal MRI scores. Otherwise, there was no significant differences in baseline infant characteristics between those infants who had normal mild, moderate or severe scores. Secondarily, they looked again, at so increased global brain abnormality and white matter injury scores. At the 36 week MRI were associated with reductions in basically all of the facets cognitive motor and language abilities at two years corrected age. And then again, that with adjustment for treatment with EBO, so when they controlled for the group when they control for gestational age recruitment site, still, each point of increased global abnormalities score was associated with a 2.5 point reduction, particularly in motor function. So motor was the most affected area, but again, it was across the board. And not surprisingly, an abnormal cerebellum score also predicted a greater effect size is specifically in motor development. So that's kind of the nitty gritty is that the MRI scan Ian's did predict the Bailey's at two years of age. And one of the points that I thought was also interesting was that gestational age was not really a predictive factor as much as weight was a predictive factor. So that I thought that was a really important point of the study. But I do think this is helping us answer the question about how do we give anticipatory guidance to parents when we get those MRIs?


Ben 20:35

Yeah, I mean, I don't have much to add, I think people should check out that figure at the end of paper, where you have this sort of three by three table. That's not a table. It's mostly graphs. And you see, the first three, the first row is the Bailey scores in relationship to global brain injury scores, and the slopes are all negative. I mean, yeah, and it's and it's the same for global brain injury for white matter score on the second row and for cerebellum score, maybe to a lesser extent, as you mentioned, for cerebellum score, but very impressive stuff. Yeah. So it's,


Daphna 21:12

well, then it begs the question again, right is do we revisit the importance of those term corrected MRIs? Which not? Not everybody's doing, especially after the the choosing wisely initiatives? So the question is,


Ben 21:26

the question is, the question really depends, it's more of a system based issue rate. Is your does your hospital have availability for MRI for neonates? Number one? And if not, is it worth the investment compared to other stuff? So yeah, I think you do have to do a close inventory of your own resources and decide what makes sense to you, depending on where you are on the ladder of sophistication and care, I guess. Because like you said, if, if you can't afford it, and if you don't need anything else more urgently, you should go ahead. If you don't, maybe there you should prioritize other things. I don't know.


Daphna 22:02

Well, and right, it's it's only as good as is as the read and so at first shout out for our pediatric radiologist and pediatric neuro radiologist specifically, is there just some fine subtle details in this neonatal neuro imaging that makes all the difference in how a study is read? And so, you know, how, like you said, having all the right resources to give the right information, but squad to see the study?


Ben 22:31

Yeah. I guess the next paper I wanted to go to was the one in JAMA. Right, the one on blood transfusions.


Daphna 22:41

So a lot of lot of buzz on Twitter about this one.


Ben 22:45

I mean, rightfully so. Number one. So the paper was published in JAMA. And I don't know if by the way, if it makes a difference, if it says JAMA Network, or JAMA, I'm assuming it's the same, but it's JAMA Network open, if people are having a hard time finding it, the link is in the show description. It's called association of blood donor sex and age with outcomes in very low birth weight infants receiving blood transfusion. first author is the powerful Ravi Patel, who is a friend of ours on Twitter. And so it's a very interesting question that is being posed right is, is the sex or age have a blood donor associated with morbidity or mortality and very low birth weight infants receiving blood transfusion? And so this, this study was was done prospectively across three hospitals in Atlanta, Georgia, they included babies who were born very low birth weight as in 1500 grams and who received blood transfusion from that's very important point exclusively male or female donors. And that's something that they mentioned in their discussion in their background as well, where prior studies did not really do this sorting, right. I mean, so many of the subject patients in the past were receiving sometimes both. So here, they only looked at patients that received it from a single donors sex rate. And, and again, the donors could have been multiple, they try to batch them together, meaning neonates were preferentially given from the same donor they will try to save the blood as much as possible, but at least from the same sex and a male donor could give to a male or a female baby, a female donor could give to a male or female baby. And the study took place between January 2010 to February 2014. And they follow these babies until 90 days or hospital discharge or transfer or transfer. So the primary outcome that they looked at were death necrotizing enterocolitis, ROP, and neck was stage two or higher, obviously ROP stage three or higher. And then the third outcome was moderate to severe bronchopulmonary dysplasia. So in total, they had 181 infants that were evaluated. The mean birth weight was 919 grams, and the mean gestational age was 27 weeks. That's So 57 infants, which was 31% received transfusions exclusively from female donors. The means the mean donor age of donor was 46.6 years. The primary outcome incidence was 21% among infants receiving RBCs from female donors and 45% from male donors. So a huge difference, right? I mean, from the primary outcome of death, neck ROP, or a severe BPD monitor with BPD was happening 21% When it was a female donor versus 45%, when it was a male donor for the typical infant who received a median of two transfusions, RBC, from exclusively female donors, compared with male donors was associated with a lower risk of the primary outcome. And the primary outcome increase as the donor age increased or decreased as the number of transfusion increased. So what we'll get, we'll get into that. So female donors had less were associated with less primary outcome. And interestingly enough, as the female donor was getting older, the outcome also decreased. So technically, you would want other females to be PRBC RBCs, or transfusion donors, right. And as the number of transfusion increased, that relationships are have tapered, obviously, that's a huge there's a huge discussion to be had as if you need so many transfusion. Aren't you so sick already that these outcomes are probably in your future? So it was difficult for them? And they mentioned that in the discussion on on, how does that contribute to the other? I'm going to stop here for a second, because I highlighted some things into discussion, obviously, and we can talk about them. But I was wondering what your thoughts were?


Daphna 26:44

Yeah, well, I mean, I'm glad they did, I admittedly, had never thought about it. And so sex, we'll talk about some of those criteria. But but really, in terms of age of donor, this was the opposite of what I hypothesized, honestly. So I thought that was very interesting. And when I think about blood donors in this country, I think most of them are coming from a I had to look it up but coming from a younger cohort. And so what do we do about? It's my first question, how can we get older females to donate blood? And or is that something we can do in our in our units to have preferential, you know, preferential for for babies? I think this is a really serious study that we have to have to talk about, because those comorbidities are significant. I'd like obviously, to see more babies, I would have liked to have seen the mixed group. So they they took out a lot of babies, I think, what close to 400 babies that have gotten from both sexes, and I imagine they would have fallen somewhere in between, but I don't know. And so I would have liked to have seen that group. But it's it's exciting information. Because you know, we do have babies, the average babies getting two, three blood transfusions in it seems to matter what kind of blood they get. So,


Ben 28:23

yeah, I did some research on stem cells. And we always preferred younger donors, somehow their cells were, I guess, quote unquote, better. And so like you said, I was very surprised to see that the older age was was more favorable. And I have no idea how you would practically implement this. Because that would mean putting away certain types of blood, then what if you don't use them? It's very tedious. But it's interesting to see that these parameters matter and outcomes of these very low birth weight infants. So interesting stuff.


Daphna 28:54

But again, I think like so many of our studies it, could it unlock other opportunities for elucidating some of these pathologies or alternative therapies. You know, when we, when we, when we see this kind of data?


Ben 29:10

Yeah, and even though it's published in JAMA, and it's 200 infants, I like that the the authors were humble enough in their conclusion to say that we're going to need larger studies to because I mean, it was a pretty large study was very well designed. So it was kind of nice. Yeah, okay.


Daphna 29:27

Very cool.


Ben 29:28

Would you want to go next?


Daphna 29:30

i Let's do this Cochrane Review. Sure. Um, so it coming from the Cochrane Library, slow advancement of enteral feed volumes to prevent necrotizing enterocolitis in a very low birth weight infants, authors, OD young McGuire. So this is kind of one of the rewrites of an earlier systematic review. So the original review included 10 studies In this current review included 14 studies, so All total, they included of just over 4000 infants in the 14 included trials. That being said, almost all of the 70% of the infants were participants in the SIFT multicenter trial for 2016. So across the trials, they came from North America, Bangladesh, Turkey, Colombia, Iran, India, South Africa and the UK. And in general, all trials, allocated babies to some range of feeds between 15 ML is per kilo per day on the low end and 40 ML is per kilo per day on the on the high end and on average, it was something between 20 mils per kilo per day versus 30 miles per kilo per day. So, not dramatic differences in the groups except in very few number of studies. And the other specifications they had is that the trials, confirmed neck radiographically and obviously, that is has potential for its own discussion again or at surgery. And so what they looked at were the primary outcomes so again, not confirmed at surgery or autopsy using standardized clinical and red radiologic criteria. At least one of the following a bilious gastric aspirate or emesis, or abdominal distension, or blood in the stool and at least one radiograph showing the mitosis or portal venous gas or free air. They also looked so neck and then all cause mortality before discharged from the hospital. And then the secondary outcomes they looked at were growth, including time to regain birth weight, and then long term growth we height head circumference, assessed at intervals from six months of age. Some of the studies also looked at neurodevelopmental disability, defined as moderate or severe developmental delay grant greater than two standard deviations below the mean. When it says to add at least 18 months, they also looked at other classifications of disability, including cerebral palsy, hearing and visual impairment, they looked at time to establish full enteral feeding time to establish oral feeding, feeding intolerance, and then invasive infection confirmed by culture, and then duration of hospital stay. So let's go. I guess we'll start with the subgroup kind of data,


Ben 32:35

the primary outcomes.


Daphna 32:40

What they looked at, let's say the subgroups of the ELB W's didn't really show an effect if you used quote unquote, small feeding volumes or quote unquote large feeding volumes, which I thought was particularly interesting. And we have the small for gestation or IUGR. Growth restricted babies. So in general also did not show an effect between small and large volumes, which I was surprised by. There are some trials that did show obviously that the smaller babies or the IUGR babies had poor feeding tolerance. The other subgroup they looked at were infants with evidence of reverse end diastolic flow in utero, and, in general did not show an effect. So that's the subgroup for the few small trials. But in general, the meta analysis of the data from the 14 trials showed that slow advancement probably does not reduce the risk of neck. So that's really their underlying message is that going slower didn't have any improved effect on the baby's having neck, the secondary outcomes and particularly growth 10 of the trials looked at that showed that slow feet advancement took obviously a longer time to regain birth weight. So that was in terms of growth, none of the trials really reported a time to establish full oral feeding. But it did show that obviously the slow advancement took longer to get to full enteral feeding. In regards to feeding intolerance. The meta analysis data from nine and the trial showed that slow advancement of enteral feed volumes may actually slightly increase the risk of feeding intolerance risk ratio 1.18. They looked at invasive infection. So meta analysis from 11 of the trials showed that slow advancement of enteral feed volumes may slightly increase the risk of invasive infection. Again, risk ratio 1.14. The confidence interval does cross one One, there was no difference in duration of hospital stay when evaluated by six of the studies. And only one of the trials reported neurodevelopmental outcomes, and children's aged 18 to 24 months, but it was the biggest trial. Again, 70% of the babies were enrolled in that SIFT, trial. And the analysis suggested that slow advancement of enteral feed volumes probably does not affect the risk of moderate or severe disability analysis of individual domains just little or no effect on visual or hearing impairment, cognitive or language delay, but suggests that slow advancement eventual feed volumes may reduce the risk of cerebral palsy slightly. So that's no small thing. I think we need more information. You know about that, obviously, more studies. But the the point of the study was really to look at neck as the primary outcome, and did babies who got maybe 30 to 40 per kilo per day advancements? Did they have higher incidences of neck? And this meta analysis says, No. And this is, again, we're rewriting our feeding protocol right now and in our in our unit. And so, can we go a little bit faster?


Ben 36:15

I'm frustrated with Cochrane.


Daphna 36:17

Why? Tell me why.


Ben 36:18

Because it's just every time I'm sorry, I have to I have to mind my manners. But I feel like a lot of the times Cochrane Reviews are published, and we get more questions than answers, right? So in this in this meta analysis, so there's less NEC, but so you think, okay, maybe I can push feedings a bit faster, but feeding intolerance is more pronounced, and babies were advanced faster? So it's like, Oh, am I gonna run into issues advancing fields? And then you say, but if I don't, eventually is fast enough, maybe invasive infections could be a problem. And so I don't know. I mean, I'm, I'm left after reading the review, wondering, should I change what we're doing? Or I feel like if I want to push the feedings a bit faster, I have a good number of reasons to do so. But I might hit a few roadblocks along the way. So I don't know. I feel like it's, it's there's a lot of these reviews that have been published recently, especially in the context of neonatology where we don't really have a good definitive answer as to where our practice should, should fall.


Daphna 37:22

Yeah, I think it just begs, again, the question that it's not a one size fits all and right, your feeding protocol, maybe for 30 weaker is not the same feeding protocol for a 23 weaker. And again, they didn't address that specifically. And, you know, are there subgroups of babies who benefit or require a slower feeding progression? And they did try to address that. But again, the studies were so few and so small, and you know, that's not my experience, I find IUGR babies difficult to feed. Right. We've had a few just in the last two weeks, where and we're, I think, an aggressive feeding group in general. And sometimes we just can't do it even if we want to. And so we just need more, we need more bigger trials and and better stratification of the groups. I think.


Ben 38:21

You're difficult, which is difficult to do, considering they're doing a meta analysis.


38:26

Right To their credit. Alright,


Ben 38:27

so the next article caught my attention is published in the Journal of parasitology. And it's called neurodevelopmental outcome of preterm infants enrolled in the Myo NOC NOC I inositol. He knows it all. I don't know how to pronounce it. randomized control trial, which is a follow up of this study that was published in 2018. in JAMA, which looked at men have to do it again minus at all effect on type one ROP right minus tau is this is this component that is important right in membrane phospholipid. And that has been thought could be helpful in managing IDs decreasing BPD. It was trials were done long time ago in the early 1990s. And it's fallen out of favor, right. But there was this trial in 2018. That looked at ROP and found really no difference in the effect of the of the medication on stage one ROP. So this is northern mental outcomes of these babies at 24 months. The reason it caught my eyes because the first author is Ira Adams Chapman, which for those of you who don't know, she's a big wig in she was a big week and there was a mental Outcome Research. And she passed away in October of 2020. And so it was very shocking to see her name as a first author, because it made me wonder, Oh, my God, like did I mistake the fact that she had passed away which I had not. And so this is sort of her the she had finished writing the paper and the paper had been submitted. And so it was it was really cool. See her work sort of continue on in the form of this paper. And they do acknowledge the fact that at the end of the paper, they acknowledge the fact that she had passed away and that she had she passed away after finishing reading of the paper. I think another one of the authors, one of the technologist also passed away, which is, which is very sad. But this was this was this was called, you know, the community, sort of the idea that your work and live live on and so so I like that. The bottom line is


Daphna 40:25

they're getting you're getting sappy on me today.


Ben 40:27

I'm not I'm not. But I mean, I mean, that was that's, that's something that we should highlight, right? I mean, this is somebody that has done a lot of good work for our community. And I think it's nice to see to see her work being published again, even posthumously. The bottom line is that the outcomes are we're no different, right? I mean, the Myo inositol was not, did not induce any changes in neurodevelopmental impairment. I think the outcomes were 60% versus 56%. The p value was not significant. And I think we can put that that, that Tibet. Anyway, I wanted to mention that paper. I thought that


Daphna 40:59

was cool. Yeah, okay. Now, we got to keep looking for other ways to provide no protection, so and negative studies or, you know, useful.


Ben 41:12

Okay, so I guess I copped out on this one, because I didn't really


Daphna 41:15

review it, it didn't really do.


Ben 41:18

So the one I wanted to talk about is a pre proof in the Journal of Pediatrics, and it's called adverse events and associated factors during intra hospital transport the newborn infants. This was a first author is Romain de la Critias. Or I think I'm butchering the name. That's okay. This is from Lausanne in Switzerland. This is a very interesting study, where they performed the prospective study to look at the frequency of adverse events during intra hospital transports. And that did not include moving a baby from delivery room to ICU, and did not include moving a baby from one hospital to the next is just like going from the unit to the radiology suite to the or back from the or, and so on and so forth. This this study took place in 2015 2017. And they defined an intra hospital transport, as we just mentioned, right for a diagnostic or therapeutic interventions. So the babies were on continuous monitoring, so they collected data before leaving on arrival. And then at some point during the transport, and they had access to heart rate, oxygen saturation, FIU to and additional measures based on other vital signs that they had during the transport. They defined an adverse event as any event considered by healthcare givers as a danger for the health of the EU more or vital signs is playing values outside reference range. And I'm not going to bore you with all the details, but they have everything defined so SATs below 85%, or temperature below 36 degrees or above 38 degrees. So you can go into that. And then the defined complication of transport through this W H O classification that says either there's no harm and the patient is not symptomatic, and there's no symptoms detected, mild harm, moderate harm, or severe harm. And again, all of these are defined in the methods. So they looked at 15. About 1500 patients were admitted to their unit during the study period. And 30 371 patients underwent 1400 transports only 293 had enough data for them to actually conduct their analysis. So that's what was included. Importantly, enough, the median gestational age was 38 weeks, right so they were not like extremely low birth weight and was not a very selected population. The most common reason for hospital admission were prematurity, congenital malformation, and asphyxia slash seizures. So the median, the median postnatal age and weight at the time of transport was 13 days and the median weight was 2900 grams. And like we said, the indications for transport are stuff we do all the time MRI ultrasound surgery returned from surgery surgery, bronchoscopy, CT and other indications. And that included like VCG is you know, which contrast and so on. So, overall, and that's something that's cool. 25% of all transports were associated with adverse events. So 25% went in for the severity of the adverse events was considered as no harm and 21% mild and 4%, moderate and point 4% And they had no severe heart which was which was, we're happy to see. patients who underwent complicated transport had lower gestational age, lower birth weight, a higher number of transport per patient, and then longer duration hospitals they compared with those who were transported without adverse events. In univariate analysis, the reason for transport a higher postnatal age longer transport transport under respiratory or hemodynamic support use of continuous infusion sedatives analgesia were associated with adverse events, medical devices, including central venous catheter, arterial catheter, gastric tubes, bladder catheter, higher number of caregivers and the type of equipment used to transport newborns were associated with adverse events during transit. words. So I think that was interesting, right? Because it's sort of it addresses this issue of a baby being in transit. And sometimes if you're not involved in the transport, it's out of sight out of mind. But these are potentially potentially harmful things that could happen to a child. And obviously, the secret the child, the more likely they are to suffer an adverse event during transport, but maybe thinking about these procedures, in more serious terms, especially when we're considering studies, right? Does a baby need to study? Does the baby need to move for that study? And so on and so forth? I think this people really sheds light on this issue that sometimes can get overlooked, because I'm saying this for myself, because sometimes you say, oh, so and so once that study, let's just get it done. Are we thinking about all these different implications? I think that was interesting.


Daphna 45:49

Well, like you said, these were not little babies, right. And this was not a transport between hospitals. So some of those things we don't have any choice about, but you can only imagine how the magnitude of events must change. The younger, the sicker, the longer the transport. So scary.


Ben 46:16

All right, I'm gonna do one more paper, and then I'll let you finish off with your last one or your last. Because I feel like I really want to get this one in. And it's called, it's a meta analysis that was published in, in pediatric pulmonology, called Digital tracheal intubation and finger palpation to confirm endotracheal tube tip position in neonates is systematic review and meta analysis. Very cool author. Yeah. First author is Dr. Rama Swami. And, yeah, I think there are doctors, right, I mean, says DM, I guess it means doctors of medicine, but anyway, doesn't matter. So if you haven't seen, we'll post a picture of what digital tracheal intubation looks like. But basically, it's framing you put your index finger all the way in the back of the throat of a baby, all the while your thumb presses on the trachea. And you're supposed to just push the tube along your index finger and with your thumb, feel the tube pass through the vocal cords. It's your finger I think works pretty much like an LMA. Yeah, yeah. And I got them. Right. That's, I mean, that's what I'm assuming.


Daphna 47:32

Yeah, no, I mean, they do it and adults, frequently, but for what


Ben 47:37

I saw, I mean, I did. We spoke about this before we came on the show, right? I mean, I didn't know this was a huge thing. I didn't know what it looked like. So I looked it up. And you see the diagram and it's like, that doesn't look right, like this shouldn't be done. And so, they did a systematic review and meta analysis of various papers who have researched the topic and they ended up including five studies, their primary outcomes was the proportion and listen to this right the proportion of successful intubations the time to successful intubation, the incidence of trauma or bleeding, and fourth the proportion of correct ATT tip position. And that was compared based on not based on x ray right it was compared based on other assessment measures like the six plus weight formula and so on. So, the thing I want to mention before we begin everything is that all the the meta analysis of the outcomes showed low certainty of evidence right. So so we have to take this with a grain of salt, but like we said, they included five studies in the meta analysis. So meta analysis of proportions showed that 94% of 94% of the digital tracheal intubations were successful in the first attempt, which to me was very surprising here, right. In the time to successful intubation with digital tracheal intubation was 7.4 second time to successful tracheal intubation was significantly shorter with digital tracheal intubation when compared to laryngoscope laryngoscope assisted intubation, and there was a difference of 4.9 seconds there was a trend toward a higher proportion of correct ATT tip positions with finger palpation when compared to weight based formula alone and again, certainty of evidence is very low. Their revision is that DTI digital tracheal intubation and finger palpation to a certain ATT position in neonates are promising strategies future study with emphasis on their learning trajectory and generalization generalizability are needed. So digital tracheal intubation did very, very well. I'm curious to hear what you think about that. Are you going to try it?


Daphna 49:42

Yeah. I'm astounded by this paper. Really, honestly. And this you know, DTI is really being taught and resource poor areas where one for intubation, two for again 82 positioning where you may not have routine regular access to X ray. But I mean 94% on the first attempt is, is significant. It really was. And I think they describe the patient population here. Did they?


Ben 50:21

The studies had a mixture of term and preterm neonates. Right. The mean gestational age was 32 weeks in studies and 28 weeks in one studies in one study, I'm sorry. And so that's that's not that's not too shabby.


Daphna 50:33

No. I mean, I think the ranges for first time intubations are somewhere between 45 and 60%, in general. So this is really something that we have to have to discuss. They also talked about its potential utility for difficult airways, maybe you know, not prenatally diagnosed, you get into into a situation where you really can't see what see what you're looking at. It's just something that we have to consider. The other thing they said, which I thought was very interesting was they looked specifically at people who had had no previous training for, for example, the positioning of the endotracheal tube, and they had similar rates. And so that in and of itself is valuable. So even if we're not going to start doing TTI is, is there a role for verifying ET tube placement where we could use less X rays, you know, especially in our smallest babies where the tube moves so much? I think that is particularly interesting. They didn't specify exactly in each paper, how they were confirming an ET tube placement. So that's a point of discussion. But I thought it was super interesting.


Ben 51:53

And it would have to be compared against other sort of major comorbidities. Yeah, like ivh, and things like that. But like you said, I mean, we've been saving laryngoscope for in our institution for less for for Haiti and other places where they have less resources, instead of just throwing them out. And this is this is a great alternative. So that was cool.


Daphna 52:16

Well, and in terms of those risk factors, I mean, they were more likely to get it on the first attempt, and they did it faster. So one might hypothesize that they might be even less risk for for those those adverse events. Yeah, very interesting. All right,


Ben 52:34

you get to close the show.


Daphna 52:35

Oh, I never get to close the show. I wanted to do this paper from pediatric research, the deluxe study, development of lung volumes during extubation of preterm infants. Lead author Lionni plus plus, Deena so this was a prospective observational study performed at the NICU in the University Hospital of Zurich in Switzerland, and data was collected as part of a kind of a six month quality control period between August 2020 and January 2021, to look at their extubation procedure. So, what they did is they used end expiratory lung impedance as a marker of functional residual capacity during the entire excavation procedure, a very preterm infants, so they they used this electrical impedance tomography, and they measured it during kind of the setup for intubation. setup for extubation, sorry, extubation. And then, in the immediate time period, post extubation, including moving babies from a supine position to a prone position. And they looked at the change from baseline of this. e li, er and expiratory lung impedance. And again, go ahead.


Ben 54:10

No, no, I was gonna say, I was gonna say the end expiratory lung impedance, because I've had to look up that term every single time, because I'm like, Oh, what is what is that again, but


Daphna 54:18

does it mean But again, as a marker of functional residual capacity, and so tell you a little bit about their group. They didn't have any predefined criteria or devices extubation performed at clinicians discretion. Infants less than 28 litre X debated to non synchronized nasal IMV. And infants greater than 28 leads for x x debated to nasal CPAP. So they didn't have any specified settings. So clinicians were able to individualize care. All their babies got a loading dose of caffeine before extubation which is something we could discuss. We could have a whole set So and then, so all patients were excavated in this supine position, and then eventually turned to prone when the nasal interface was secured in place. And so I think looking at this, there first really, figure one is very cool, very cool. And so they measured the electrical impedance, but they also looked at the global changes. So the change from baseline, they looked at heart rate, oxygen saturations and SPO, two or 502 ratios during these pre specified events, which I will indicate. So immediately before first handling of the infant, so they got a baseline measurement, they did tracheal suctioning, this I thought was super important the start and end of adhesive tape removal. And you know, I just put up a fit in our new unit that we didn't adhesive remover, we now have adhesive remover. So I'm very pleased about pulling the endotracheal tube. So the actual act of extubation initiation of non invasive ventilation immediately before moving the baby to prone position, and then immediately after turning the baby to prone position. And then they looked at 10 minutes after turning to prone position. So they're prone 10.


Ben 56:20

So it was it was really cool for them to break down the procedure, right? For sure. All these different steps, right? They're never, when you put it like this, it makes it such a big deal that's like, Oh, my God, all the steps. But it's true. We have to go through all these things. And they even mentioned that, on average, it took 18 minutes. 18 minutes. Yeah, right. And so you're like, that's true. It takes that is true. But


Daphna 56:40

you're always like, I'll just go and I'll just do it before shift change, or I'll do it before rounds. And it always takes the whole Yeah. So I mean, the nitty gritty. And again, I think this graph is so useful, it really just you can really see visually, the difference between the change in the e li for each scenario


Ben 57:04

that's going on Twitter, by the way. That's right. So the biggest


Daphna 57:07

decrease in this I was so validating for me in ELA occurred between adhesive adhesive tape removal, beginning and adhesive tape removal ending. So just let that sit for a while they didn't even take the tube out. But it's so disruptive to these babies to start removing the tape. And you know, they they're I think their time between tape and extubation is pretty small, which is I think what happens in most units. And then there were significant changes in SPO. Two, mainly attributable attributable to decreases again at adhesive tape removal during extubation. And then the placement of the non invasive ventilation. So so the biggest decrease in EMI, I told you a bit between tape removal, and then the biggest increase so how do they recoup their functional residual capacity occurred between the supine and prone positioning. So I thought that was a really important point. And they do that for all of their babies when they excavate them, they flip them over. Importantly, so they lose quite a bit of their EMI again, tape further decreases with extubation we pretty much stay the same once you place the nasal IMV. And again, they were placing in NIV after excavation so they discuss that. But what I was really, really impressed to see is that babies seem to regain regain their FRC pretty quickly. In fact, 40% of FRC loss was recouped within the first 10 breaths of nasal IMV. And after turning infant prone so in this graph, so they really recouped all of their EMI basically, even before they flipped the baby and then flipping the baby actually improved. The Ely a positive change from baseline and that persisted even at the 10 Minute prone mark. So some of the things they discussed is you know, how can we minimize the FRC loss and one of the things they recommend which we do in our unit is the they called it pre pap. So putting on the non invasive device just before removing the endotracheal tube so you're getting peep throughout the whole procedure. I would have loved for them to show us those measurements, you know to redo the experiment and show us those measurements. And then hear me out about this. Maybe we take the tape off and we let these babies chill out for a little bit. ripping their tubes out. I just think, again, if we take a really developmentally focused approach to extubation, we should let these babies recover a little bit between taking the taking the tape off and moving forward with extubation. And then certainly thinking about how positioning can change our lung capacities. So I thought it was a super cool paper. I think it's something people can start using today. Some of this information.


Ben 1:00:33

Yeah, I agree. No, yeah, I have a lot. I have a lot of thoughts. Actually, I think it's a great paper. Number one, the pre prepping that you're talking about? I think it's something that we do that is extremely, extremely helpful. Yeah. And I don't know how successful they are in this institution, because they mentioned that they do nasal intubation. Right. So I mean, the tube is in the near the ET tube. So that's true. Institution, you're orally intubated. So I feel like it's much more convenient, because what you can do is you can set up the nasal prongs, you can set up everything before you start touching the tube. And then you're able to then remove the tube and not have any loss or interruption in ventilation. Which brings me to my second point, which is this is best case scenario, right? How many times that there's an event malfunction, that there's like something where the calibration has to be redone,


Daphna 1:01:24

the prongs didn't fit, or they have you know, their their safety pins are lost, their tape is lost. Right?


Ben 1:01:33

And so you can only imagine number one if number one, you can only imagine the how dramatic the loss of FRC is. If you have complications, I remember vividly one day I had like a new respiratory therapist, and the vent just didn't work. And we had to sort of use a new puff. But I'm saying things can go wrong, and can go terribly wrong as this thing is happening. And then do you just do you just torpedo the whole extubation process because you had a baby that was ready, and you've recruited so much, and it's impossible for them to actually get back up to that level of, of recovering their FRC. So I think I think that's that's very interesting. And the last point I wanted to make is this idea of prone, right. I mean, sometimes I had not thought of automatically putting everybody prone. That is something that that definitely seems to be worthy of doing. Again, great graphs, something Dr. Jensen spoke about. Big graph is always makes a paper pop. And that was that was a good example of that.


Daphna 1:02:40

Yeah. But I was happy to see how quickly they re recruited. I did not envision that in a million years that I would see that effect. So that gave me some hope that even if even if the excavation takes longer than you expect that that hopefully they'll get there.


Ben 1:02:58

Yeah. And, and again, like we said, initially, the idea of breaking down the indexation process into these steps, I think brings more attention to each one of them and doesn't make it sound like every one of them is point three seconds. It takes a long time to do it. And it has physiologic implications. So yeah, that was cool.


Daphna 1:03:16

It's a it's a procedure in and of itself. explanation. Alright. All right. So should we, we've we've come to the end. Should we do some of our Twitter feedback?


Ben 1:03:28

Yeah, let's do Twitter feedback. We've over overstepped our time again, but that's okay. And there's there were more papers, but for next time, I guess.


Daphna 1:03:36

All right. Well, we again, we really appreciate the buzz on Twitter and your individual messages keep them coming. But this was a tweet. Dr. Kashif Ahmad, love the new at Nikki podcast, the isolette noise discussion is on point. We've worked with industry to try and cancel noise and isolettes and published simulated results. And there's a link actually to their article, which was really cool and does describe this device about kind of mitigating amplified noise applied for at NIH funding to evaluate this device in infants. So let's just keep the conversation going. For sure.


Ben 1:04:17

Yeah, yeah, that's good. That's the exciting part of Twitter is that again, we're not familiar with the whole literature, and to be able to have people connect with us and share their their papers or research. It's exciting. Anyway, that was awesome.


Daphna 1:04:30

All right, buddy.


Ben 1:04:32

Well, see you next week, guys. Thank you so much. Definitely have a good one. Okay. Thank you for listening 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. Nikki 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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