#327 - 🫀 From the Heart - It's Complicated

Hello friends 👋

In this episode of From the Heart, Dr. Nim Goldshtrom and Dr. Adrianne Bischoff walk through a complex neonatal case involving sudden decompensation shortly after birth. With few early clues and no clear diagnosis, the team discusses how to approach circulatory shock, differentiate pulmonary hypertension from congenital heart disease, and manage critically ill neonates before imaging is available.

Using this case as a reverse journal club, the hosts break down relevant literature and decision-making pathways: when to start prostaglandin, when epinephrine makes sense even without low blood pressure, and why relying only on numbers like MAP can be misleading. They also examine the role of therapeutic hypothermia in unstable infants and the potential cardiovascular consequences of cooling.

Later, the conversation focuses on left ventricular dysfunction, balancing systemic and pulmonary circulation via the ductus, and using bedside markers like lactate and perfusion to guide treatment when echo isn’t immediately available. The episode closes with thoughts on autoregulation, cerebral protection, and the evolving role of emerging technologies in neonatal hemodynamics.

A real-world deep dive into diagnostic uncertainty, evolving physiology, and decision-making under pressure in the NICU.

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

Blood pressure:

Barrington KJ. Common hemodynamic problems in the neonate. Neonatology. 2013;103(4):335-40. doi: 10.1159/000349933. Epub 2013 May 31. PMID: 23736012.

Dempsey EM, Barrington KJ, Marlow N, O'Donnell CP, Miletin J, Naulaers G, Cheung PY, Corcoran D, Pons G, Stranak Z, Van Laere D; HIP Consortium. Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns. Neonatology. 2014;105(4):275-81. doi: 10.1159/000357553. Epub 2014 Feb 27. PMID: 24576799.

Dempsey EM. What Should We Do about Low Blood Pressure in Preterm Infants. Neonatology. 2017;111(4):402-407. doi: 10.1159/000460603. Epub 2017 May 25. PMID: 28538235.

Autoregulation and blood pressure in HIE:

Howlett, J. A., Northington, F. J., Gilmore, M. M., Tekes, A., Huisman, T. A. G. M., Parkinson, C., Chung, S. E., Jennings, J. M., Jamrogowicz, J. J., Larson, A. C., Lehmann, C. U., Jackson, E., Brady, K. M., Koehler, R. C., & Lee, J. K. (2013). Cerebrovascular autoregulation and neurologic injury in neonatal hypoxic-ischemic encephalopathy. Pediatric Research, 74(5), 525–535. https://doi.org/10.1038/pr.2013.132

Burton, V. J., Gerner, G., Cristofalo, E., Chung, S. en, Jennings, J. M., Parkinson, C., Koehler, R. C., Chavez-Valdez, R., Johnston, M. v., Northington, F. J., & Lee, J. K. (2015). A pilot cohort study of cerebral autoregulation and 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. BMC Neurology, 15(1), 1–13. https://doi.org/10.1186/s12883-015-0464-4

da Costa CS, Czosnyka M, Smielewski P, Austin T. Optimal Mean Arterial Blood Pressure in Extremely Preterm Infants within the First 24 Hours of Life. J Pediatr. 2018 Dec;203:242-248. doi: 10.1016/j.jpeds.2018.07.096. Epub 2018 Sep 20. PMID: 30243537. 

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

Dr. Adrianne Bischoff Hi everyone. Today on From the Heart, it's complicated. We are tackling a challenging neonatocardiac case. So Nim and I thought that this would be a great opportunity to walk through our thought process, break down the physiology, discuss some of the key decision points, and explore some of the nuances of managing critically ill neonates. Kind of what Nim and I were talking just before we started recording is like doing a journal club but backwards.So we're hoping that through our discussion of these cases that we will do every once in a while, we can bring some of the literature so that it's not just what Nim and I think, but actually having some science behind why we do the things the way that we do and why do we think about things the way that we think about things. Is that right, Nim?

Dr. Nim Goldshtrom Yeah, evidence-based medicine in practice, right? Reading an article and applying it is great, and what a great way to show you everyone how we think and work, right? How we apply the evidence of practice and go backwards from a case towards that evidence.

Dr. Adrianne Bischoff Cool. So let's just dive right in. So for today's case, we have a 39 plus one weeks infant that was born by spontaneous vaginal delivery. The baby was born vigorous, but had a history of thin meconium stained fluid. And the Apcar scores were eight at one minute. And then again, at five minutes was eight again. The baby was put on mom's chest and about at seven minutes of life, the baby was noted to be dusky.So the team brought the patients to the warmer and put the SAT probe and the baby was satting 30 % on room air. So at that point in time, PPV with oxygen supplementation were initiated and they did not notice any significant improvement in the saturations. So the baby was subsequently moved onto the NICU, ended up getting intubated at about 30 minutes of life, was given a normal saline bolus and a transfer call was initiated to a level three unit. By the time that the transfer call was started, the baby had already received surfactant for whatever reason. And at the time of the call, the baby was on mechanical ventilation with pressure, sorry, with volume control at seven mils per kilo, a PEEP of six, a rate of 30, and the FiO2 was set to 90%.The gas that was most recent done at that time was an arterial gas, had a pH of 6.9, a PCO2 of 67, a PO2 of 27 with a base deficit of 20. And when we asked for a set of vitals, the baby's heart rate was 160. The blood pressure, which was being measured through an umbilical artery catheter was 69 over 56. And the lactic acid was 10.2.So Nim, when you start listening to me going through this case, what are some of your key concerns at this stage?

Dr. Nim Goldshtrom Yeah, I'm so happy that this baby is alive and doing fairly well, but you have severe acid on a gas on a ventilator with a lactate of 10, right? This is shock, right? You just have to define which version of it may be distributed, but you're describing the versions of like a cardiogenic shock or mixed shock picture with hypoxic acidosis. so sure, pulmonary hypertension is one of the first things to think about, congenital heart disease.some kind of failure of transition and just poor dysfunction, either septic or cardiogenic in nature. And so it's great initial information to things I'd want to know from here is, let's get a pre and post-ductal saturation if we can get that for blood pressures. Look at the saturation differential. What about signs for cardiac output and systemic delivery of oxygen and blood, perfusion signs? Do we have a lung exam, x-ray findings, other supportive data that could help us?

Dr. Adrianne Bischoff Yeah, so I have kind of limited information because obviously this was at a time of the transport call. I don't have four point blood pressures. They just were too confused and worried about the baby and that was just not reasonable to ask at that point. They just had a UAC and that's what they were giving us. Pre and post ductal sats at this point after the baby had been intubated, the pre ductal sats was in the 70s.and the post ductal sats were in the mid fifties. The baby did look kind of shocky. So the pulses were, they were okay, but the baby kind of looked a little mottled, had poor perfusion. Obviously it's too early in the baby's life to assess for urinary output and things, but there, does seem like there are signs of poor systemic perfusion. And the x-ray was not particularly exciting. There was... No obvious cardiomegaly. The lung fields seem appropriate, maybe a little TTN-ish at this point in time. Hard to say. They didn't show us an x-ray before they gave surfactants. So we could have a whole discussion about why would you give surfactant to a term kid with this type of presentation, but I don't have enough information to delve into that. So we talked about... the differential diagnosis kind of going into shock, sepsis, pulmonary hypertension, congenital heart disease. And I think the first article that I wanted to bring up for discussion at this point of the case is how do we differentiate in our minds as neonatologists in a hypoxemic baby if this is more likely to be of cardiac origin, meaning congenital heart disease origin, or if this is more likely to be in the spectrum of pulmonary hypertension with normal cardiac anatomy. So we're gonna put all the articles that we'll talk about, we will link in the show notes later on. But the first article is not new, it's from 2010. I'm not even going to attempt to say the name of the authors, because that would be rude. But this was the group in Toronto who looked at patients in the transport setting.that were hypoxemic and they were trying to define what was the accuracy essentially of clinically guessing between pulmonary hypertension and congenital heart disease. So they looked at this question and they classified the babies in either suspected congenital heart disease, suspected pulmonary hypertension or questionable based on a combination of history, physical exam, lab tests, chest x-ray and the initial response to treatment.They have a nice table that I recommend people look at it, which doesn't have anything that would be extremely surprising for people, but I think it is a very good review, especially for the trainees. And some of the highlights that they may point you towards one diagnosis or the other. So for example, for congenital heart disease, they have having other dysmorphic features, a murmur being very common, weak pulses being very common.a big difference between the blood pressure between the right arm and the legs, which obviously I don't have in this case, an absence of changes in the saturations when weaning oxygen. So a baby whose sats are in the 70s in 100 % of oxygen and you keep trying to wean the oxygen and their sats are still in the 70s, that's probably more likely to be cardiac than to be lung related and pulmonary hypertension related, cardiomegaly on chest X-ray.So those are all kinds of things that make you think more about congenital heart disease. And things that may make you point more towards pulmonary hypertension in the transitional period specifically will be a history of fetal distress, low Apgar scores, poor pH, a baby that is very labile when you're handling, a baby that when you do try to wean the oxygen, the sats get even worse.and the very commonly abnormal lung parenchyma because obviously pulmonary hypertension is a vascular disease, but the majority of the neonatal cases of pulmonary hypertension do have associated lung disease. So basically using these parameters, they were actually pretty accurate in about 88 % of the cases, which I thought was pretty interesting that we can guess pretty well even in the absence of a lot of information at that point. So I'm gonna put this back on you, Nim.With the information that I have provided to you so far, what are you thinking when you're looking at this case? Do you think this is more likely to fall in which of the categories?

Dr. Nim Goldshtrom So just on what we have so far on these things, it's hard for me to guess. There is bad pH on this kit. There's severe metabolic exosus and lactates. Just from my own practice, I am always concerned about ductal-dependent lesions. But they usually don't present so acutely. There's only a handful of congenital heart diseases that will collapse within the first 30 minutes of life when you don't recognize them.So those are obstructed pulmonary veins, which can look a lot like this kind of picture. Transpositions who have poor mixing. But this child has a saturation. I'm sorry, had FIO2 in the 90%. And I don't know if they ever saturated normally. And hypoplastic left hearts who have restricted atrial symptoms. And this child could fit in that picture potentially. But it doesn't feel like what we see in clinical practice other than like obstructed TAPDR. And those kids look terrible, which this could be.I don't actually have a good guess. I don't know if this is one of those classic three severe CHD types that present like this versus PPH. Without more data, I'd have a hard time yet perfectly differentiating this. But let's get some more data and see where this could be.

Dr. Adrianne Bischoff Yeah, that's great. I agree. I think this baby kind of fits a little bit into both sides of that table from the article. And that's exactly what the team thought. They were like, doesn't fit 100 % with, I am pretty confident that this is pulmonary hypertension and I'm going to give nitric, but it didn't 100 % fit with congenital heart disease either. So in the absence of knowing exactly what was going on, the decision was to, okay, let's start prostaglandin.and let's give some epinephrine given the history of shock, even though the blood pressure was maintained, which I think was a good thing. And we can talk about that too, but I don't think that you need to start medications for cardiovascular support only on the basis of numerical hypotension. I think this baby had enough signs for poor cardiac output that is reasonable to start epinephrine at inotropic dose.So they started prostaglandin at 0.03 to maintain ductal patency. And they started epinephrine at 0.05 for presumed cardiac dysfunction. And due to the potential of congenital heart disease, the decision was made to not start nitric oxide at that point in time during transport. And then the baby was transported to a higher level of care. So on arrival in the NICU, the baby was already almost four hours of life. By that point,throughout transport, the FIO2 had been slowly weaned and was now down to 60%. The pre-ductal sats were in the mid to high 90s and the post-ductal sats were in the low 80s. The lactate had improved to 3.3 and remember that it was 10.6 in the beginning of the case. The chest x-ray was consistent with what was described to be a little bit of venous congestion, but no overly exciting signs for anything else.And because of the history, the post-natal history of having what seemed like an asphyxia event, even though not right around the time of delivery, but right after delivery, the baby was examined, had a Sarnit with hypoxia, the acidosis, and an abnormal neurological exam that was consistent with a moderate encephalopathy. The baby was deemed to qualify for therapeutic hypothermia.Now with this information, with this baby that has just arrived to your NICU, let's go through a couple of questions. Do you think now with the information that you have, you can classify this baby more likely into one or another bucket? And would you consider, for example, now the use of inhaled nitric oxide?

Dr. Nim Goldshtrom Great questions. And I do have an answer and I don't know if it's either of those two, but I just want to reiterate how important what two of the things you just said were is that not waiting right for other hard markers to start shock medications is so vital. You labeled again, you're reporting on this case from an outside hospital with a blood pressure of 69 over 56. And so you have a map that's probably somewhere in the low 60s. The nuance there.right, is you have an acidotic patient with a pH of 6.9 and a lactate of 10 and a narrow pulse pressure with a normal quote unquote map for age. This is compensated shock by definition. There is no point in waiting. You absolutely need to start something and not assume that the baby is going to resolve. Right. And I 100 % agree with you. I would have started something. I agree. I will use Epi, right. Just assume that there's cardiogenic shock. This kid is near uncompensated shock because you have narrow pulse pressure.trying to maintain SVR high in the face of almost certainly low cardiac output, they need beta and inotropy rapidly, right? And it's very weird because you have a heart rate of 160, you have a normal to high blood pressure that's narrow and a lactate of 10. It can look like it's not as dangerous as it is, but this is about to collapse and arrest physiology. And so that's an excellent point. Like there is no more data you should need to try to recognize compensated shock, right? Which is just holding onto your vitals.before you end up collapsing.

Dr. Adrianne Bischoff I will add to that before you move on that also I don't want people to think that we start these drugs and we keep escalating on them rapidly, especially epinephrine, right? Epinephrine has a profile that the type of action that it has on the neonate is dose dependent and at low doses like which was what was started here, the main...main action will be on inotropy, which is what we were aiming for. But if you keep escalating, especially once you're getting to 0.1 and more doses, then you're gonna start having a lot of alpha adrenergic effects and you can increase the SVR, which in a kid that has evidence that they are already doing a good job with their SVR, you might actually make things worse. remember, we're not treating the number, but we're treatingthe patient and we have evidence that using this dose, irrespective of what the blood pressure was, you can see that I didn't even mention what the blood pressure was at this point, because it's irrelevant, because everything else is pointing towards the baby is better. The lactate is better, the saturations are better, the perfusion is better. So I just wanted to make that point about the dosage of the medication.

Dr. Nim Goldshtrom Yeah, absolutely. And again, I'm sure I'm speaking to everyone who knows this, you know, you're just going to be watching this baby very closely and doing very frequent assessments of the exam, lactates and gases. And if you have at your disposal, again, we're not pitching brands here, but we use near-infrared scoscopy as a regional site monitoring, particularly of the lower body. We use renal, other people use abdomen.as a trend marker for the venous oxygenation system to complete the VO2-DO2 circuit. And for us, we do find it helpful in picking up early signs of shock and then the recovery of shock when you're probably resuscitate if you use those in your markers. And so as you mentioned, you've got the patient four hours later on a lower FIO2 now with a pre and post-ductal gradient, but having high SATs pre-ductally, low SATs post-ductally, and venous congestion.And so without labeling this as a disease and condition, what I see here is right, some kind of arch flow issue, right? You are using the duct because you're unoxygenated blood from the right heart through the duct into the descending aorta, almost certainly in providing some degree of mixing, which is why your lower body is more desaturated than your upper body. And you have signs of venous congestion. And so if you can't send enough blood out of the left side of your heart, where the duct and the right side of the heart has to contribute partly and your pulmonary vessels are congested, right? To me, that story fits with your left side has failed for some reason. And there's maybe a mixed picture here, right? Like this feels like almost coarctation, right? You have a pre post ductal gradient with lower limbs. And if there were four extremity blood pressures, we would hear about that too.but something about the left heart isn't doing so well, and it seems like maybe the right heart is contributing in some fashion, either right from the pulmonary vasculature itself or the RV as in offloading for more flow to the lower extremities.

Dr. Adrianne Bischoff Yeah. I think though it's important for people to hear the story though, because I get the impression, maybe I'm wrong and the audience will let us know when they listen to this and when they comment on whether they like this case or not. But I feel like a lot of neonatologists would have jumped into the immediate most common thing, which is I have a baby who is asphyxiated, who's in a lot of oxygen. I'm thinking of diseases of the right side.And that venous congestion on x-ray could be easily be mistaken or read as, well, this is TTN or this is RDS or this is meconium aspiration. And people may not be thinking quite with this mindset that the LV might be an issue and maybe just thinking, well, I think this is an asphyxiated baby with pulmonary hypertension that is on a lot of oxygen and maybe I should treat with a pulmonary vasodilator. Right?

Dr. Nim Goldshtrom Yes, I agree. think that is almost certainly the most likely picture to kind of like put together, right? People with ductal saturations, a kid who was in shock, right? A kid who had acidosis and you're just recovering from a shock state. And those would probably be extremely reasonable things to do without imaging, without seeing complex kids who have like that. And I'm sure most people without any further data would have. would do that and that's probably the right clinical thing to do in this clinical picture, right? Is to assume the most common is common and a failed transition with wet lungs and what looks like PPN physiology, you know, when you don't yet have a screening thing to figure out if this is, you know, TAPVR masquerading as itself is potentially that. Again, the reason I pointed out the left side failure, and again, in my practice to kind of put the thing is that it's not that weird for kids to have...Lackadies of 10, right, when there's severe failed transition, where there's intrauterine distress, when you come out with cord gases that are disastrous, right, and you need heavy resuscitation at birth, which is not the story, but this kid decompensated very quickly. It is just strange that the therapy for PPHA is not epi, and that you gave epi. And that's the only reason I went to this left-sided thing, is right, that this team that you're describing tried something that is not a direct pulmonary hypertension medication and saw clinical improvement.And so sometimes that data helps, right? If Epi was on and the lactate stayed the same and the pH never changed, then the pathology would have changed completely. And it's only because you told me the story of Epi and lactate clearance and the presumption of a quote unquote improved clinical state that I jumped to that first because you're right. In my mind, it was like, PPHN, failed transition, lungs are probably trash, but everything's just shunting right to left, which is why you're mixing. And that could explain the gas. But then again, the heart could have been stunned and maybe that's why the Epi is helping.PPHN that turned into cardiogenic shock. It is confusing, my bias was, while the epi did so well, maybe this is shock, maybe this is a mixed picture. And so this is fascinating. I wonder where this goes next.

Dr. Adrianne Bischoff Yeah. And I think along those lines, what would have been the more traditional train of thought, again, we would be thinking this is an asphyxiated baby that we're going to start cooling. So first of all, what would be the most common or the most natural pathway, which is pulmonary hypertension, heart dysfunction, which most commonly would be right heart dysfunction in the setting of pulmonary hypertension, but also in HIE itself, right? We have Dr. Giesinger's work, both at the Blue Journal and then subsequently on archives, where she evaluated a big group, prospectively, of patients with HIE undergoing cooling. And right heart dysfunction had never been really documented as a big thing in HIE until she did it, especially in the amount of details that she did it with quantitative measurements of RV dysfunction. And not only that,was the predominant phenotype seen in patients with HIE, but also having right heart dysfunction was significantly associated with worse outcomes, both in the short term in terms of mortality and worse neurological outcomes and bad brain MRI, but also for the survivors in terms of long-term neurodevelopmental outcomes. So I think the normal would have been for people to think, well, this is pulmonary hypertension.RV dysfunction and maybe people could argue, well, you gave Epi, you might have improved the RV. But I will counter that to the fact that the RV dysfunction in patients with HIE, if you don't treat the afterload problem to the RV, which is the pulmonary vasculature, typically does not improve this fast in a matter of two hours without doing any pulmonary vasodilator, just giving Epi towhat frequently are dead RVs that we see on echo in these asphyxiated babies does not result in this significant improvement in both their saturations as well as their perfusion and lactate and so on and so forth. Is that your experience as well, Nim?

Dr. Nim Goldshtrom Yeah, absolutely. And this is, again, something that we both see in different ways and a high degree. And the clinical exposure and experience gives us these insights to kind of translate back certain things that get better in certain periods of time. pH crises after cardiac surgery, for example, have this arc of desaturation that's very different from a respiratory desaturation or a pure right to left cardiac desaturation. And you get used to kind of looking at it over time. So I agree, right? This is a different arc of recovery than you would have expected. And for a kid who is just going to have pure dysfunction as a problem.

Dr. Adrianne Bischoff And along the same lines, since we're talking about HIE and cooling, what's your experience or what do you typically see in terms of heart function when you do start the cooling process? Do you see something that suggests that it might make the baby worse from a cardiovascular standpoint? What's your take on that?

Dr. Nim Goldshtrom I mean, absolutely. mean, the literature is rife with those papers, right, of both LV and combined ventricular dysfunction while on cooling. Again, this is more, again, not evidence-based in terms of hard research, but our clinical practice is that many of our kids have to go either on no-renone or epi or dobutamine, depending on which ventricle is struggling more during cooling, for maintaining a kind of like good cardiac output if they're having periods of both...We're out of type of hypertension, right? Because cooling is also going to create a lot of more veins or contractive states. But we're trying to support LV or RV recovery. so most of them will go on Milrinone. Again, I think some people will discuss in a second because they're normotensive, but you're experiencing both cardiac dysfunction and still lactate clearance issues. So you can tolerate the afterload effects of Milrinone while you're allowing for lucetropy and some gentle inotropy. But yeah, it's a very common... described event of cardiac dysfunction on cooling.

Dr. Adrianne Bischoff Yeah. And your colleague there, Angelica Vasquez, who was our trainee here, she did a small study when she was a fellow here at the University of Iowa in 2024. And she published on the Journal of Perinatology, which we're also going to link on the show notes, looking at 10 babies that had TN echoes before cooling and after cooling. So to see specifically the effect of cooling, there were no other differences in therapies that were used between those two.kind of short interval echoes. And what she saw was that post-cooling was associated with worsening markers of pulmonary hypertension and PVR with a decrease in cardiac output and some decrease in heart function, although that was not quite as significant in this very small cohort. But I think that that's another important point, even it's not really the discussion of this case, but when you do have those really, really, really sick babies,I think it's important to know that cooling might actually make things worse. And this might be a little bit controversial and it's still a little bit tricky, but I personally think that sometimes we rush into cooling as quickly as possible, you know, because we want to protect the brain, which obviously is important. But I will argue that if then the baby decompensates very quickly and he's in 100 % barely hanging themselves and then you start cooling and now their sats are bad.and they have to end up on ECMO or they die because of a pH crisis, we're not doing them a great service either. So I tend to be a bit more slow in the cooling until I have at least some degree, as much as possible, of course, of clinical stability from a cardiorespiratory standpoint, because I think it makes the whole process a little bit smoother and it decreases the chance of decompensating. And then we can go into, you know, do you cool and do you put on ECMO while you cool and all of that stuff, which... is probably a little bit too much for this discussion, but happy to listen any of your thoughts on this.

Dr. Nim Goldshtrom No, it's true. mean, cooling is engaging in further critical care, right? Like the body under those degree and conditions is not going to be better, right? The liver is not going to be happy. The heart is not going be happy. You have to have control. It's a semi-procedural and bringing towards the target of 30 degrees is an active process. You don't just turn it on like a light switch and you have to make sure that you have cardiac control, respiratory control.matching of DO2 and VO2 and good sedation so the patient is not in distress and demanding more. It is no less challenging, right, of getting them on and making sure that they're on it comfortable, safely and protected from the cells to gain the benefit of it. Because you're right, right, getting into it quickly without feeling that you have good control of watching the patient and making sure they're not decompensating is as actively important to do as making the decision itself, right, to go to cool or not to go.

Dr. Adrianne Bischoff Yeah, I typically, when I'm running transport calls, I typically recommend that the outside providers, not necessarily my transport team, but that the outside providers maintain normal thermia in most patients. And that's a twofold reason. Number one is that frequently I found in my experience that outside providers are not used to cooling and they just turn off the warmer. And if the baby's truly asphyxiated, they tank their temperature. So unless they can...truly keep an eye on the warmer and monitor the temperature, I would rather them not cool and just wait for my team to get there. So that's reason number one. But then also from a stability standpoint, that if they're gonna start cooling, the PVR might start going up and they might not have all the resources because they might be in places where they don't have nitric or where they won't have the expertise or the availability to do the escalation of a cardiorespiratory support that a baby might need.should they start getting worse upon initiation of therapeutic hypothermia. So that's usually my practice.

Dr. Nim Goldshtrom Absolutely. You have to know your system. Cooling on transport is possible, but you have to know how well the baby is going to be supported before you get there, whether you have the resources and team to continue to support them effectively while cooling on transport and to get them into your unit. So it's definitely a art and systemic change that many places will have to undergo.

Dr. Adrianne Bischoff All right, let's go back to this case then. So, okay, the question that everybody wants to know, what did the echo show? What is the diagnosis? So you are correct, Nim. And this baby did have severe left ventricular systolic dysfunction. This baby had an ejection fraction of 38%. For those that are not quite used to echo numbers, normal would probably be more than 55 to 60 % in a neonate. The baby had low cardiac output with a left ventricular output of 65. Having said that, in cooling babies, I frequently findrelatively common low left ventricular outputs, but not 65. Maybe in the nineties is fairly normal, but 65 is probably lower than I would have expected. The baby also had mild right ventricular dysfunction, but the left heart dysfunction was much more pronounced than the right. There was an unobstructed aortic arch. There was no structural heart disease. The four pulmonary veins were draining normally.The coronaries were fine. And at this point on epinephrine of 0.05 and prostaglandin of 0.03, there was a large PDA which measured five millimeters, which was chanting bidirectionally. So how do we approach? Now that you know what you know, now that you have a diagnosis, how do we approach severe LV systolic dysfunction with low cardiac output?in a baby that has this presentation and is on these medications. What are your thoughts?

Dr. Nim Goldshtrom You know, feed and grow, just feed and grow. No, we kid, obviously. Just to reiterate though, some of the points that you're bringing up with the echo and then the clinical picture. You know, if we're presenting a case with you know, spot numbers once a moment in time, but you know, even with like the description of like, sure pre and post-doctoral SATs and congestion and like my running to left side of dysfunction, almost certainly this kid was going to be desaturated.during periods of time in the unit. And this almost certainly would have looked like PPHN, and even I may have started nitric on there. The caution I have in cases is the echoes are super helpful, but anytime I see an x-ray, right, in the story of a kid who is fine, fine, fine, and very quickly fell apart after being on mom's chest, my fear is always, just like you said, pH or CHD. And when the diagnosis could potentially be obstructed veins,or pH and my x-ray is weird, I'm always just hesitant on just trying pH first because it would make it worse. And then I run to the function algorithm to say, well, let's just support the heart until we can get an echo because that's what I'm definitely afraid of. So it's such a problem that two diseases look so much the same and one therapy will fix one and the same therapy will make another one disastrously worse. And to kind of like, youObviously not everyone has immediate availability to do echo and this pilot had to move to the center to get it. And this is sadly the fate for a lot of obstructed TAPVRs who are born postnatally in centers that are low risk that then have to be rapidly escalated before you can find a diagnosis. And everyone's stuck in this place, right? Do you start nitrate? Do you not? And to that point, I just want to go back to the very first things, Normal heart rate, narrow pulse pressure, normal blood pressure and high lactate start in eye neutral.That is shock by definition. Whether after that you're debating, well, there's DSATs and it could be nitric plus shock. Yes. And there's a good chance that in our center, if this kid was born like this and we couldn't get an echo right away, we would have done everything, right? Epi and nitric and waited and got an echo. And now that you're displaying, right, open duct bidirectional shrunting with severe LV dysfunction as like the probability of physiology, this will take time. Part of the reason is why did the kid go into shock, right? What is happening anatomically? I would want to know, again, you have no structural heart disease, which is great, and you're describing normal veins, normal coronaries, which is the other important stuff, no corructation, arches are obstructed and not hypoplastic. You don't have quote unquote, Shonesy-like picture with small mitral valves and small number of structures. It really is a just normal heart that's in shock. This is going to take time, right? And again, there's, there's... Literature a little bit about this like what's the right drug of choice right? No, we're to beauty mean an epinephrine I don't think I'm up to date on like the most important studies about like which one has the best efficacy for Not just heart recovery, but let's say heart recovery in the fast architecture the most appropriate thing to some degree, right between all those three drugs whatThe most important thing I think about is that they offer you options. They offer you options for normal tension LV dysfunction, and they offer you options for hypotension normal function. And they allow you to choose between, I have hypotension and I need beta and alpha. Great, that's epi. I have more more tension, but the function's really bad and I gotta get this heart pumping quickly. Dobutamine. And I've got like dysfunction with normal tension and it's...both LV and maybe RV and maybe Milano could be helpful. Like it's the broad thinking I have on this. How do you take these drug classes in your armament and use and is there evidence that you use more to try to drive more toward one drug choice or another for these kinds of conditions?

Dr. Adrianne Bischoff  Yeah. I will say that between the butamine and epi, my clinical practice, again, is similar to yours. It's dependent on the blood pressure and also the degree of dysfunction for mild, moderate heart dysfunction, whether LV or RV, where the blood pressure is normal or just maybe a little bit low. I think the butamine is fine. It's a cleaner drug. It will confuse people less.there will be less confusion with the potential of hyperglycemia and high lactate that sometimes epinephrine comes as a side effect, not necessarily related to the actual underlying heart dysfunction. For severe dysfunction or for babies who are hypotensive, I tend to go with epi just because you get more banked for your buck. But I don't think either of them is wrong. If you only have one, if you're more used to using one, I think that's fine. I try to not use the butamine much more than five to 10 mikes per kilo per minute. If I get 10 and I'm not really seeing improvement in my heart function or my perfusion markers, I tend to switch to Epi. Again, just for more bang for the buck. I feel like escalating anything more than 10 of the butamine, you end up just getting too much chronotropy without much more improvement in cardiac output or in stroke volume. Epi, I just caution again what I mentioned in the beginning. It is a dose dependent drug as well. So if I'm using it for inotropy, I don't want to escalate more than 0.1 because I don't want to make things worse from an alpha receptor standpoint. But then I'm going to throw here a little caveat on the Murinone side, which was my project. I'm going to toot my own horn here, which is probably not very kosher, but I'm gonna do it anyways.

Dr. Nim Goldshtrom It's research. It's research or an expert in. Go for it.

Dr. Adrianne Bischoff where we looked at babies with hypoxemic respiratory failure who had pulmonary hypertension that received Mironone as an adjunctive therapy for that on top of nitric. And we compared three groups, essentially cooling babies, non-cooling babies. And in cooling babies, in a very small group, we had a lot of trouble using Mironone in cooling babies. our...cohort. I mean, they were not all the babies, but some babies were so severely hypotensive with Mironone. And we just have to remember that Mironone is renally excreted. Babies with HIE are more prone to have AKI than they are also not peeing for because of SIADH. And who knows what therapeutic hypothermia also does to the clearance of the medication.but we just saw a couple of patients who had catastrophic hypotension and needed significant escalation in other vasopressors to recover from, I'm talking about single digit blood pressures. They all survived, but they had worse outcomes and they needed higher inotropic score. So we are quite worried about using marinone in cooling babies and we don't because we're fearful.Have you said that? Since I've published that, I know of many centers who do use it and I don't have enough data because it was such a small sample. It is very possible that that effect is only in the babies who really have severe AKI or whose blood pressure was kind of already borderline when it was started. I don't have that nuance or that degree of expertise, but here at Iowa, we are quite fearful of using Murinone.during therapeutic hypothermia. So it's a drug that we don't typically use. So in cooling babies with HIE, if I need inotropic support, we will go with either dubutamine or epi while they are cooling. And then we will reserve myrinones for once the therapeutic hypothermia has resolved. What about if they are hypotensive on either of these drugs? Yeah. Then what? Do you use a vasopressor on top? What is your, or do you keep escalating? What's your usual approach?

Dr. Nim Goldshtrom Now, again, you bring up great points right there. There's pros and cons to milrinone. Continued hypertension does suggest that other parts of the system aren't working. And so the cardiovascular system is interesting, and it's built in wonderful ways. Preload, contractility, afterload. And you're fixing a certain amount of things with inotropes. Volume and fluid shifts are not typically so common where they need extra volume resuscitation. And so then the assumption is that a child who is maybe mildly sedated and or in recovery from shock probably has vasoplegia, right? This is not uncommon from kids who present with various forms of distributive shock, right? Or multi-compartment cardiogenic shock. This is exactly how they present with severe shock after congenital heart surgery, right? It's volume and inotropes that we use first. And when they're still hypertensive, we assume that there's refractory.Vasoplegia and star pressure so things like vasopressin is a very common thing that we would need right if we need to have more alpha Because as you're saying if you're going up on epi to a certain degree you're getting alpha You're just not getting direct alpha like you would with another drug You know You could probably use a little bit of nor epi and epi if you needed to or or go to much harder drugs like phenylephrine if you really really need to get squeeze and so yes, right if you're continuing to have With what you believe is either imaging guided right echoes the show. I'm getting good squeeze I am getting better contractility than I was before and I know chokeAnd I don't have a heart that's collapsing on itself and that's suggesting that I have low preload and I'm not volume responsive, right? So I'm not in the preload recruitable curve of the cardiac output scale. The assumption has to be that you have some vasoplegia, right? And you should probably give some low dose, know, afterload increaser, like Fezopressin or Norepinephrine to help you through this period until more of the inflammatory reactive cascade is resolved.

Dr. Adrianne Bischoff Can you educate us a little bit more, Nim, on blood pressure targets and auto regulation in this type of patient?

Dr. Nim Goldshtrom Oh boy, this is Keith Barrington's world, right? And he spent a career doing it and he still hasn't given us a good answer, right? What's the blood pressure to do? But there are really interesting and novel things coming to get forward. know, like we were all looking forward to the hip trial, right? We tried to stop a little bit early because of recruitment issues and it's a problem, but I think new technology is giving us some answers. So, you know, in the mid 2010s, some groups from both Texas And Hopkins were looking at auto-regulation, right? It's now a feature that we can use to guide what blood pressure looks like as it reacts to the brain. And so Jennifer Lee's group out of DC and Hopkins looked at therapeutic hypothermia, right? They looked at what auto-regulation using things like meters, devices, and blood pressure to evaluate what is optimal blood pressure in this group while cooling, going on to cooling, while cooling, and after cooling, and neurodevelopmental outcomes. And so...The first interesting thing, again, these studies will be on the website, that they noted is optimal blood pressure for term neonates, whose gestational age was hovering around 40 in this prospective study, was around 50, low 50s, 51 plus minus. So if you think about what we all use and maybe used to something different, like gestational age equals map, there still has not been a great deviation from, you target the 10th percentile or do you target the 50th percentile for a better outcome?try to first do no harm and most of us will probably use the GA equals MAP equation as like this is good enough. What's really fascinating and there are preterm articles and we'll have one available on the site as well, which are the preterm infants, right? In the first transitional period have the same physiology, right? Our assumption that GA equals MAP is not what the brain wants. Preterm infants between 24 and 28 weeks, cerebral auto-regulatory plateau, right? Where the safe portion of the auto-regulatory phases is approximately 10 points.above their gestational age during the transitional period. But again, there's not yet studies that are suggesting that targeting this, living in that number is yet associated with some different or improved outcome, right? It's just the currently associations that what the brain wants is actually much higher than what our numbers about 50th or 10th percentile are about. And what's fascinating about Dr. Lee's study in her group is that they saw a small association with MRI findings at two years of age.And that particularly during the cooling and the rewarming phases, more time spent above the lower limit of auto regulation, right, in the optimal map were associated with less white matter injury in these kids. Again, not that they intervened on them, right, but that they just tracked their auto regulatory blood pressure curve, about where they were and how close they were to the lower limit. And that more time spent above was, quote unquote, safer for brain injury. So these are fascinating studies about what the future could hold for us. And we certainly need more prospective studies. So if you target that blood pressure and if you drive it toward that number, are you making a meaningful impact? And more importantly also, are you not causing other problems, Like brain bleeds and further injury to the brain. We certainly do some of that practice here. I gently have moved my marker slightly above gestational age because you're already on an inotrope for a child recovering from heart disease. Like what is the marginal difference between a MAPA 40 and a MAPA 45 for a full term kid?But again, I'm worried that if I ask my group to kind of target these higher numbers that the auto regulatory literature suggests, it will increase therapeutic creep without a lot of evidence. I think we have to just be cautious about waiting for more studies that actually show utility and value like there are in adults after traumatic brain injury where they're already into those studies. But yeah, I don't yet deviate away a lot from GA equals math because of the... fear of therapeutic creep without a lot of strong evidence to say that I'm doing something more positive than if I just aim for a map and that I'm not going to increase the therapeutic load that's going to make it harder for me and my team to work back on. And then I don't know that the child is gaining necessarily more utility until we get more research on outcomes.

Dr. Adrianne Bischoff Yeah, I think that those are all great points. And along this similar line is how much do you want to fix the problem, right? We know from Dr. Giesinger's that RV dysfunction is associated with worse outcomes. But is it that the RV dysfunction is just a marker of the severity of the hypoxic insult and therefore these babies are more likely to have worse outcomes? Or is it thatif we fix their heart function and therefore we improve their cardiac output, that might actually improve white matter injury and brain outcomes as well. And to that extent, how much do you fix it, right? What's the optimal level, not only in terms of blood pressure, but in terms of cardiac output, because we also wanna prevent these babies from having reperfusion injury. So we don't wanna go from a state of... low cardiac output from their heart dysfunction and from their asphyxia event to now going to supranormal cardiac output that might worsen the reperfusion injury itself. So I think there's just so much that we don't know. And I agree with you, it's hard to implement new things based on numbers that we're seeing in terms of vital signs when we don't have enough prospective studies and physiological studies to kind of tease that out.

Dr. Nim Goldshtrom Yeah, that's, in my opinion, one of the landscapes of the future, right? We all have a lot of nice new fancy shiny tools and numbers and data points. And they definitely offer clearly value added, right, above the things that we're doing. The integration and the ability to get them into studies, right, across multiple centers so that we can power these things to get the answers faster is the challenge, right?Hemodynamics isn't available, it's not available in a lot of places. And I'm sure, I'm guessing, but I'm sure, I might guess, that the hemodynamics community still probably has a challenge in trying to say, let's all do this study this year and share our data and combine patients and get the numbers, not for the IRB or all that stuff, just because it's hard. It is just hard to collect all those things. And that's what it's going to take, right? This kind of approach where like, what answer, what question do we want to answer this year?Every center get us 50 babies, let's get 500 and boom, we can answer this question. Because that's the kind of effort that it'll take, right? Autoregulation is the same way. Only a few places have these technologies, you have to pull them together. But this is where we should all be striving for, right? If there's new tools on there, how do we get the patients who are exposed to them into databases and systems where we can get those answers faster? This should be one of the promises of AI, right? Helping us link massive data faster, quicker, try to get answers from stuff that exists. And it's just separated by distance, time, and network cables, essentially.

Dr. Adrianne Bischoff 100%. So let's go back to our case. So here we have our asphyxiated baby with kind of unexpected left heart dysfunction. So I think what I would classify as the core priorities when managing this baby, first of all, obviously supporting myocardial function. In this case, we're going to do optimizing inotropy, which we said we could do epi, we could do the butamine.I personally wouldn't do Miranone, but that's up for debate. I think another core priority is to think about myocardial oxygen demand. Obviously this baby is already cooling and is already intubated, but if this is a baby that is extremely agitated or that is in pain for whatever reason, I want to make sure that we're targeting that as well, because I don't want to put any additional stress in this physiology.in a severe LV dysfunction where the RV was actually not that bad, there is a role for maintaining ductal patency because functionally this works like a hypoplastic left heart almost, where you actually want right to left shunt in order to support the systemic circulation. So I don't want this baby to set a hundred percent because at that point in time I might be switching my ductal shunt.to be more bidirectional or to be more left to right and I'm not gonna be supporting flow. I would prefer to have blue flow than to have pink blood with no flow, which ends up being a gray baby. I would always rather have a blue baby than a gray baby.

Dr. Nim Goldshtrom

Correct. True hearts cannot be said. Blue is always better than gray.

Dr. Adrianne Bischoff Correct. And along the same lines, we want to make sure then through that PDA that we are balancing the pulmonary and the systemic circulation. So doing things that will help promote some degree of right to left shunt, which may include PEEP, may include slightly higher CO2s, may include even lower oxygen targets, depending on the severity of the situation, until that LV starts recovering.And we will know that as the days go by, if your lactate keeps improving and now your split is getting closer together in terms of pre and post ducto saturations, that might be a clue that the LV is recovering and the circulation is no longer as dependent on that right to left flow. But I will manage this baby with sequential echoes to decide when I can take the PGE away and then when I can take the epinephrine down or even off.

Dr. Nim Goldshtrom No, it's a great summation. The only thing I can add to this great rubric, right? Support the heart, decrease your demand. A duct can be used for a lot of things, not just to be closed in a preemie or to be kept open in CHD, is time can be your friend and your enemy. And it's your friend when you're just constantly reevaluating. This physiology would change and will get better. And the ductal gradient would eventually disappear. And so when your sats are eventuallypre-end post in the high 90s, you could get an echo, but you probably know that you don't really need it right away, and you may want to start moving towards closing the duct, right? You've offloaded the LV, the function is better. And so use this dynamic picture and use the clinical tools, kind of like we mentioned, heart rate, blood pressure, lactate, shock, start treatment. The images are great, not everybody has access to them all the time, and there's lots in the clinical assessment of us watching a child evolve over time.that allow you to say like, yep, now we're using the duck. And it's like, now it looks like the shunt usage has diminished and maybe we're promoting too much pulmonary overcirculation. Now it's time to let the duck close and use time as your friend to both help in the therapy and understand if you're not meeting the targets that you're at.

Dr. Adrianne Bischoff Yeah, absolutely. I think these are the type of babies that keep me up at night, but they're also the ones that push us to being better clinicians.

Dr. Nim Goldshtrom

Literally and metaphysically where I keep us up at night

Dr. Adrianne Bischoff Yeah. So for the audience, if you enjoyed this discussion, if you enjoy this format, please let us know. Send us your thoughts, your cases, your questions. You might hear them in future episodes of From the Heart.

Dr. Nim Goldshtrom Yeah, absolutely. Thank you for joining this. This is great. We enjoyed it and we hope you do as well. And we'll see you all next time for more real cases and real challenges and real time learning in neonatal hemodynamics. Take care.

Dr. Adrianne Bischoff Thank you.