#461 - [🫀 From The Heart] - Blue Baby, Gray Baby: Severe LV Dysfunction Masquerading as PPHN

Hello friends 👋

A term newborn looks fine on mom's chest, then crashes within minutes. By the time transport arrives, there's a pH of 6.9, a lactate over 10, and a baby already intubated and on surfactant. Is this pulmonary hypertension, congenital heart disease, or something else entirely? In this episode of From the Heart, It's Complicated, Dr. Adrianne Bischoff and Dr. Nim Goldshtrom work through a real, complex neonatal cardiac case in real time, the kind of case that keeps neonatologists up at night. They break down how to clinically differentiate PPHN from congenital heart disease with limited data, why epinephrine's response mattered more than the blood pressure number, how therapeutic hypothermia can unmask cardiac dysfunction, and why "blue is always better than gray" when managing a shunt-dependent circulation. Along the way: real literature, real physiology, and the reasoning behind decisions made under pressure, with a surprise diagnosis at the end.

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Articles:

1. Accuracy of clinical diagnosis and decision to commence intravenous prostaglandin E1 in neonates presenting with hypoxemia in a transport setting. Shivananda S, Kirsh J, Whyte HE, Muthalally K, McNamara PJ.J Crit Care. 2010 Mar;25(1):174.e1-9. doi: 10.1016/j.jcrc.2009.04.005. Epub 2009 Jul 3.PMID: 19577418

2. Impaired Right Ventricular Performance Is Associated with Adverse Outcome after Hypoxic Ischemic Encephalopathy. Giesinger RE, El Shahed AI, Castaldo MP, Breatnach CR, Chau V, Whyte HE, El-Khuffash AF, Mertens L, McNamara PJ.Am J Respir Crit Care Med. 2019 Nov 15;200(10):1294-1305. doi: 10.1164/rccm.201903-0583OC.PMID: 31251076

3. Neurodevelopmental outcome following hypoxic ischaemic encephalopathy and therapeutic hypothermia is related to right ventricular performance at 24-hour postnatal age. Giesinger RE, El Shahed AI, Castaldo MP, Bischoff AR, Chau V, Whyte HEA, El-Khuffash AF, Mertens L, McNamara PJ.Arch Dis Child Fetal Neonatal Ed. 2022 Jan;107(1):70-75. doi: 10.1136/archdischild-2020-321463. Epub 2021 May 27.PMID: 34045280

4. Impact of therapeutic hypothermia (TH) on echocardiography indices of pulmonary hemodynamics among neonates with hypoxic ischemic encephalopathy (HIE). Vasquez AM, Bischoff AR, Giesinger RE, McNamara PJ.J Perinatol. 2024 Aug;44(8):1212-1215. doi: 10.1038/s41372-024-01958-8. Epub 2024 Apr 2.PMID: 38565651 No abstract available.

5. Hemodynamic response to milrinone for refractory hypoxemia during therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. Bischoff AR, Habib S, McNamara PJ, Giesinger RE.J Perinatol. 2021 Sep;41(9):2345-2354. doi: 10.1038/s41372-021-01049-y. Epub 2021 Apr 13.PMID: 33850285

6. Hypotension in Preterm Infants (HIP) randomised trial. Dempsey EM, Barrington KJ, Marlow N, O'Donnell CPF, Miletin J, Naulaers G, Cheung PY, Corcoran JD, El-Khuffash AF, Boylan GB, Livingstone V, Pons G, Macko J, Van Laere D, Wiedermannova H, Straňák Z; HIP consortium.Arch Dis Child Fetal Neonatal Ed. 2021 Jul;106(4):398-403. doi: 10.1136/archdischild-2020-320241. Epub 2021 Feb 24.PMID: 33627329 Free PMC article. Clinical Trial.

7. Cerebrovascular autoregulation and neurologic injury in neonatal hypoxic-ischemic encephalopathy. Howlett JA, Northington FJ, Gilmore MM, Tekes A, Huisman TA, Parkinson C, Chung SE, Jennings JM, Jamrogowicz JJ, Larson AC, Lehmann CU, Jackson E, Brady KM, Koehler RC, Lee JK.Pediatr Res. 2013 Nov;74(5):525-35. doi: 10.1038/pr.2013.132. Epub 2013 Aug 13.PMID: 23942555 Free PMC article.

8. A pilot cohort study of cerebral autoregulation and 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. Burton VJ, Gerner G, Cristofalo E, Chung SE, Jennings JM, Parkinson C, Koehler RC, Chavez-Valdez R, Johnston MV, Northington FJ, Lee JK.BMC Neurol. 2015 Oct 20;15:209. doi: 10.1186/s12883-015-0464-4.PMID: 26486728 Free PMC article.

9. Wavelet Autoregulation Monitoring Identifies Blood Pressures Associated With Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy. Liu X, Tekes A, Perin J, Chen MW, Soares BP, Massaro AN, Govindan RB, Parkinson C, Chavez-Valdez R, Northington FJ, Brady KM, Lee JK.Front Neurol. 2021 Apr 28;12:662839. doi: 10.3389/fneur.2021.662839. eCollection 2021.PMID: 33995258 Free PMC article.

10. Optimal Mean Arterial Blood Pressure in Extremely Preterm Infants within the First 24 Hours of Life. da Costa CS, Czosnyka M, Smielewski P, Austin T.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 (00:00:248)

Hi everyone. Today on From the Heart, It's Complicated, we are tackling a challenging neonatal cardiac case. Nim and I thought 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. What Nim and I were talking about just before we started recording is that this is kind of like a journal club, but backwards. We're hoping that through discussing these cases, which we'll do every once in a while, we can bring in some of the literature so that it's not just what Nim and I think, but that there's actual science behind why we do things the way we do and why we think about things the way we do. Is that right, Nim?

Dr. Nim Goldshtrom (00:38:000)

Evidence-based medicine in practice. Reading an article and applying it is great, and this is a great way to show everyone how we think and work — how we apply the evidence in practice, going backwards from a case toward that evidence.

Dr. Adrianne Bischoff (00:50:000)

Let's dive right in. For today's case, we have a 39-plus-1-week infant born by spontaneous vaginal delivery. The baby was born vigorous but had a history of thin meconium-stained fluid. The Apgar scores were 8 at one minute and 8 again at five minutes. The baby was placed on mom's chest, and at about seven minutes of life the baby was noted to be dusky. The team brought the baby to the warmer, placed a saturation probe, and the baby was satting 30% on room air. At that point, positive pressure ventilation (PPV) with oxygen supplementation was initiated, with no significant improvement in saturations. The baby was subsequently moved to the neonatal intensive care unit (NICU) and 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 the transfer call was started, the baby had already received surfactant, for whatever reason. At the time of the call, the baby was on mechanical ventilation with volume control at 7 mL/kg, a PEEP of 6, a rate of 30, and the FiO2 (fraction of inspired oxygen) was set to 90%. The most recent gas, an arterial gas, had a pH of 6.9, a PCO2 of 67, a PO2 of 27, with a base deficit of 20. When we asked for a set of vitals, the baby's heart rate was 160, the blood pressure — measured through an umbilical arterial catheter (UAC) — was 69/56, and the lactate was 10.2.

So Nim, as you're listening to me go through this case, what are some of your key concerns at this stage?

Dr. Nim Goldshtrom (02:03:402)

I'm so happy this baby is alive and doing fairly well, but you have a severely acidotic gas on a ventilator with a lactate of 10. This is shock — you just have to define which version of it. Maybe distributive, but you're describing something more like a cardiogenic or mixed shock picture, with hypoxia and acidosis. So, pulmonary hypertension is one of the first things to think about — congenital heart disease, some kind of failure of transition, and poor ventricular function, either septic or cardiogenic in nature. It's great initial information. The things I'd want to know from here: let's get pre- and postductal saturations if we can, four-limb blood pressures, look at the saturation differential. What about signs of cardiac output and systemic oxygen delivery — perfusion signs? Do we have a lung exam, X-ray findings, other supportive data that could help us?

Dr. Adrianne Bischoff (03:50:690)

I have kind of limited information because this was at the time of the transport call. I don't have four-limb blood pressures — the outside team was too worried about the baby, and it just wasn't reasonable to ask for that at the time. They only had a UAC, and that's what they were giving us. Pre- and postductal sats at this point, after the baby had been intubated: preductal sats were in the 70s, postductal sats were in the mid-50s. The baby did look kind of shocky — pulses were okay, but the baby looked a little mottled with poor perfusion. It's too early in the baby's life to assess urine output, but there do seem to be signs of poor systemic perfusion. The X-ray wasn't particularly notable — no obvious cardiomegaly, lung fields seemed appropriate, maybe a little TTN-ish (transient tachypnea of the newborn) at this point, hard to say. They didn't get an X-ray before giving surfactant, so we could have a whole discussion about why you'd give surfactant to a term infant with this presentation, but I don't have enough information to delve into that.

So we talked about the differential — shock, sepsis, pulmonary hypertension, congenital heart disease. The first article I wanted to bring up is how we differentiate, as neonatologists, whether a hypoxemic baby is more likely to be of cardiac origin — meaning congenital heart disease — or more in the spectrum of pulmonary hypertension with normal cardiac anatomy. We'll link all the articles we discuss in the show notes. The first article isn't new — it's from 2010. I won't attempt the authors' names, but this was a group in Toronto who looked at hypoxemic patients in the transport setting, trying to define the accuracy of clinically guessing between pulmonary hypertension and congenital heart disease. They classified babies as suspected congenital heart disease, suspected pulmonary hypertension, or questionable, based on history, physical exam, lab tests, chest X-ray, and initial response to treatment.

They have a nice table — nothing surprising, but a very good review, especially for trainees. For congenital heart disease: other dysmorphic features, a murmur being very common, weak pulses being very common, a big blood pressure difference between the right arm and the legs — which I don't have in this case — an absence of change in saturations when weaning oxygen (a baby whose sats stay in the 70s in 100% oxygen despite weaning is more likely cardiac than pulmonary), and cardiomegaly on chest X-ray.

Pointing more toward pulmonary hypertension in the transitional period: a history of fetal distress, low Apgar scores, poor pH, lability with handling, worsening sats when weaning oxygen, and commonly abnormal lung parenchyma — pulmonary hypertension is a vascular disease, but most neonatal cases have associated lung disease. Using these parameters, they were accurate in about 88% of cases, which I thought was interesting — that we can guess fairly well even with limited information.

So I'll put this back on you, Nim. With the information I've given you so far, which category do you think this case falls into?

Dr. Nim Goldshtrom (09:16:280)

On what we have so far, it's hard for me to guess. There's a bad pH in this kid, severe metabolic acidosis, and a high lactate. From my own practice, I'm 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 without being recognized: obstructed pulmonary veins, which can look a lot like this picture; transposition with poor mixing — but this child had an FiO2 in the 90s, and I don't know if they ever saturated normally; and hypoplastic left heart with a restrictive atrial septum, which this child could potentially fit, but it doesn't feel like what we typically see clinically, other than something like obstructed TAPVR (total anomalous pulmonary venous return) — and those kids look terrible, which this could be. So I don't actually have a good guess whether this is one of those three classic severe congenital heart disease presentations versus PPHN. Without more data, I'd have a hard time differentiating perfectly. Let's get some more data and see where this goes.

Dr. Adrianne Bischoff (11:40:000)

That's great — I agree. I think this maybe fits a little into both sides of that table from the article, and that's exactly what the team thought. They were like, it doesn't fit a hundred percent with "I'm confident this is pulmonary hypertension, I'm going to give nitric oxide," but it didn't fit a hundred percent with congenital heart disease either. So, without knowing exactly what was going on, the decision was: let's start prostaglandin, and let's give some epinephrine given the history of shock — even though blood pressure was maintained, which I think was a good thing, and we can talk about that too. But I don't think you need to start medications for cardiovascular support only on the basis of numerical hypotension. I think this baby had enough signs of poor cardiac output that it was reasonable to start epinephrine at an inotropic dose.

Dr. Adrianne Bischoff (12:10:488)

They started prostaglandin E1 (PGE1) at 0.03 mcg/kg/min to maintain ductal patency, and started epinephrine at 0.05 mcg/kg/min for presumed cardiac dysfunction. Due to the possibility of congenital heart disease, the decision was made not to start inhaled nitric oxide at that point during transport, and the baby was transported to a higher level of care.

On arrival at the NICU, the baby was almost four hours of life. Throughout transport, the FiO2 had been slowly weaned and was now down to 60%. Preductal sats were in the mid-to-high 90s, postductal sats were in the low 80s. The lactate had improved to 3.3, remembering it was 10.2 at the start of the case. The chest X-ray was consistent with mild venous congestion but no other notable findings. Because of the postnatal history — what seemed like an asphyxial event, though not right around delivery but shortly after — the baby was examined and had a Sarnat exam consistent with hypoxia and acidosis, and an abnormal neurological exam consistent with moderate encephalopathy. The baby was deemed to qualify for therapeutic hypothermia.

So now, with this information — the baby that's just arrived to your NICU — let's go through a couple of questions. Do you think you can now classify this baby more confidently into one bucket or another? And would you consider, now, the use of inhaled nitric oxide?

Dr. Nim Goldshtrom (14:29:388)

Great questions, and I do have an answer, though I don't know if it's either of those two buckets. I want to reiterate how important two of the things you just said are: not waiting for other hard markers to start shock medications is vital. You reported this case from an outside hospital with a blood pressure of 69/56 — so a MAP (mean arterial pressure) probably somewhere in the low 60s. The nuance is: you have an acidotic patient with a pH of 6.9, a lactate of 10, and a narrow pulse pressure with a normal, quote-unquote, MAP for age. This is compensated shock by definition. There's no point in waiting — you absolutely need to start something and not assume the baby's going to resolve on its own. I agree with starting epi — assume there's cardiogenic shock. This kid is near uncompensated shock because of the narrow pulse pressure. Trying to maintain a high SVR (systemic vascular resistance) in the face of almost certainly low cardiac output — they need beta and inotropic support rapidly. It's strange because you have a heart rate of 160, a normal-to-high but narrow blood pressure, and a lactate of 10 — it can look less dangerous than it is, but this is close to collapse-and-arrest physiology. There's no more data you should need to recognize compensated shock — vitals holding on right before collapse.

Dr. Adrianne Bischoff (16:26:314)

I'll add to that — before you move on — I don't want people to think we start these drugs and keep escalating rapidly, especially epinephrine. Epinephrine's effect on the neonate is dose-dependent. At low doses, like 0.05, which is what was started here, the main effect is on inotropy, which is what we were aiming for. But if you keep escalating, especially once you get to 0.1 mcg/kg/min and beyond, you start getting a lot of alpha-adrenergic effects and can increase SVR, which in a kid whose SVR is already doing a good job might actually make things worse. So we're not treating the number, we're treating the patient — and we have evidence that using this dose, irrespective of what the blood pressure was — you'll notice I didn't even mention the blood pressure at this next point, because it's irrelevant when everything else is pointing toward the baby getting better: the lactate is better, the saturations are better, the perfusion is better. I just wanted to make that point about medication dosing.

Dr. Nim Goldshtrom (17:30:000)

Absolutely. And again, you're just going to be watching this baby very closely with frequent exams, lactates, and gases. If you have it available — we're not pitching brands here — we use near-infrared spectroscopy (NIRS) as a regional site monitor, particularly of the lower body. We use renal; other people use abdominal placement as a trend marker for the venous side of the oxygenation system — completing the VO2/DO2 (oxygen consumption/oxygen delivery) circuit. We do find it helpful in picking up early signs of shock and its recovery once you're properly resuscitating, if you have those markers available.

Dr. Nim Goldshtrom (18:34:400)

So, as you mentioned: patient four hours later on a lower FiO2, now with a pre- and postductal gradient — high sats preductally, low sats postductally — and venous congestion. Without labeling this as a specific disease yet, what I see here is some kind of arch flow issue. You're using the duct — sending unoxygenated blood from the right heart through the duct into the descending aorta, almost certainly providing some degree of mixing, which is why the lower body is more desaturated than the upper body, and there are signs of venous congestion. If you can't send enough blood out of the left side of the heart, the duct and right heart have to contribute partly, and the pulmonary vessels get congested. To me, that story fits with the left side having failed for some reason, and there may be a mixed picture — this feels almost like coarctation: a pre-postductal gradient with lower-limb desaturation. If we had four-limb blood pressures, we'd probably hear about that too. Something about the left heart isn't doing well, and it seems the right heart may be contributing, either from the pulmonary vasculature itself or the RV offloading additional flow to the lower extremities.

Dr. Adrianne Bischoff (19:10:000)

I think it's important for people to hear the story, because I suspect — and the audience can let us know when they listen — that a lot of neonatologists would jump to the most common thing: an asphyxiated baby needing a lot of oxygen, thinking of right-sided disease. That venous congestion on X-ray could easily be misread as TTN, RDS (respiratory distress syndrome), or meconium aspiration. People may not be thinking that the LV (left ventricle) could be the issue, and might just think, "this is an asphyxiated baby with pulmonary hypertension on a lot of oxygen — maybe I should treat with a pulmonary vasodilator."

Dr. Nim Goldshtrom (19:40:870)

I agree — that's almost certainly the most likely picture to put together: pre-postductal saturations, a kid in shock, a kid with acidosis just recovering from a shock state. Those would be extremely reasonable things to consider without imaging, without seeing complex cases like this, and most people without further data would do that — and that's probably the right clinical call in this picture: assume the most common thing is common, a failed transition with wet lungs and PPHN-like physiology, when you don't yet have a way to screen for something like TAPVR masquerading as PPHN.

The reason I pointed to left-sided failure — and this is just my practice — is that it's not that unusual for kids to have lactates of 10 with severe failed transition, intrauterine distress, disastrous cord gases, and heavy resuscitation at birth — which isn't this story, but this kid decompensated very quickly. It's just strange that the standard therapy for PPHN isn't epinephrine, and epinephrine is what was given. That's the only reason I went toward the left-sided issue — this team tried something that isn't a direct pulmonary hypertension medication and saw clinical improvement. Sometimes that data helps: if epi had been started and the lactate stayed the same and the pH never changed, the underlying pathology would look completely different. It's only because you told me the story of epi plus lactate clearance and a presumed improved clinical state that I jumped to that — because in my mind it was, "well, PPHN, failed transition, lungs are probably trashed, everything's shunting right to left, which explains the mixing and the gas" — but then again, the heart could have been stunned, and maybe that's why the epi is helping. So it could be PPHN that turned into cardiogenic shock. It's confusing, but my bias was: the epi did so well, maybe this is shock, maybe it's a mixed picture. This is fascinating — I wonder where this goes next.

Dr. Adrianne Bischoff (21:51:788)

Along those lines, the more traditional train of thought would be: this is an asphyxiated baby, we're going to start cooling. What would be the most natural pathway — pulmonary hypertension, RV dysfunction, which most commonly shows up as right heart dysfunction in the setting of pulmonary hypertension, but also in HIE (hypoxic-ischemic encephalopathy) itself. There's Dr. Giesinger's work, both in the Journal of Pediatrics and subsequently in the Journal of Perinatology [journal names as stated by the speaker; exact citation unverified — see Flags], where she prospectively evaluated a large group of patients with HIE undergoing cooling. Right heart dysfunction had never really been documented as a major feature of HIE until she did this, especially with the level of detail using quantitative measurements of RV dysfunction. Not only was it the predominant phenotype seen in patients with HIE, but right heart dysfunction was also significantly associated with worse outcomes — both short-term, in terms of mortality and worse neurological outcomes and abnormal brain MRI, and for survivors, in terms of long-term neurodevelopmental outcomes.

So I think the "normal" thought process would be: pulmonary hypertension, RV dysfunction. Someone might argue, "well, you gave epi, maybe you improved the RV" — but I'd counter that RV dysfunction in HIE patients, if you don't treat the afterload problem to the RV (the pulmonary vasculature), typically doesn't improve this fast — in a matter of two hours — without any pulmonary vasodilator. Just giving epi to what are frequently near-akinetic RVs on echo in these asphyxiated babies doesn't usually produce this significant an improvement in saturations, perfusion, and lactate. Is that your experience too, Nim?

Dr. Nim Goldshtrom (23:59:502)

Absolutely. This is something we both see in different ways, and the clinical exposure gives us these insights to translate back — certain things get better in certain time frames. Pulmonary hypertensive crises after cardiac surgery, for example, have an arc of desaturation that's very different from a respiratory desaturation or a pure right-to-left cardiac desaturation. You get used to looking at it over time and differentiating the two. I agree — this is a different arc of recovery than you'd expect for a kid whose only problem was pure PPHN.

Dr. Adrianne Bischoff (24:40:000)

Along the same lines, since we're talking about HIE and cooling — what's your experience with heart function once you start the cooling process? Do you see anything suggesting it could make the baby worse from a cardiovascular standpoint?

Dr. Nim Goldshtrom (26:00:812)

Absolutely — the literature is full of papers on both LV and combined ventricular dysfunction during cooling. This is more clinical experience than hard evidence, but many of our patients end up on milrinone or epinephrine/dobutamine, depending on which ventricle is struggling more during cooling, to maintain adequate cardiac output if they're having periods of relative hypotension — because cooling also tends to create a more vasoconstricted state, or we're trying to support LV or RV recovery. Most will go on milrinone. I think we'll discuss this in a second, because they're often normotensive but still having cardiac dysfunction and lactate clearance issues, so you can tolerate the afterload-reducing effects of milrinone while getting the benefit of lusitropy and some gentle inotropy. It's a very commonly described phenomenon — cardiac dysfunction during cooling.

Dr. Adrianne Bischoff (27:00:000)

Your colleague there, Angelica Vasquez — our trainee here — did a small study as a fellow at the University of Iowa in 2024, published in the Journal of Perinatology, which we'll also link in the show notes. She looked at 10 babies who had targeted neonatal echocardiograms (TNE) before and after cooling, to see specifically the effect of cooling itself — there were no other differences in therapies between the two short-interval echoes. She found that post-cooling was associated with worsening markers of pulmonary hypertension and pulmonary vascular resistance (PVR), with a decrease in cardiac output and some decrease in heart function, though that wasn't quite as significant in this very small cohort.

I think that's another important point — even though it's not the direct focus of this case — when you have really, really sick babies, it's important to know that cooling itself might make things worse. This might be a little controversial, but I personally think we sometimes rush into cooling as quickly as possible, because we want to protect the brain, which is obviously important. But if the baby then decompensates quickly — is at 100% oxygen and barely hanging on — and then you start cooling and their sats worsen and they end up on ECMO (extracorporeal membrane oxygenation) or die from a pH crisis, we're not doing them a service either. I tend to be a bit slower to cool until I have at least some degree of cardiorespiratory stability, because I think it makes the whole process smoother and decreases the chance of decompensation. Then we can get into whether you cool and ECMO simultaneously, which is probably too much for this discussion — but happy to hear your thoughts.

Dr. Nim Goldshtrom (28:45:000)

It's true — cooling is engaging in further critical care. The body under those conditions isn't going to be happier; the liver isn't going to be happy, the heart isn't going to be happy. It's semi-procedural, and bringing the baby toward the 32-degree target is an active process — you don't just flip a switch. You have to ensure cardiac control, respiratory control, matching of DO2 and VO2, and good sedation so the patient isn't in distress and demanding more. It's just as challenging to get them onto cooling comfortably, safely, and protected from themselves as it is to make the decision to cool in the first place. Going into it quickly without confidence in your control, or without watching the patient closely for decompensation, is just as critical as the decision to cool or not.

Dr. Adrianne Bischoff (29:58:936)

When I'm running transport calls, I typically recommend outside providers — not necessarily my own transport team, but the outside providers — maintain normothermia in most patients. Two reasons: first, outside providers often aren't used to cooling and may just turn off the warmer, and if the baby is truly asphyxiated, their temperature tanks. Unless they can truly monitor the temperature closely, I'd rather they not cool and wait for my team to arrive. Second, from a stability standpoint — if they start cooling, PVR might rise, and they may not have the resources, such as nitric oxide, or the expertise, to escalate cardiorespiratory support if the baby worsens on initiation of therapeutic hypothermia. That's usually my practice.

Dr. Nim Goldshtrom (30:20:000)

Absolutely — you have to know your system. Cooling on transport is possible, but you need to know how well the baby will be supported before arrival, whether you have the resources and team to continue supporting them effectively while cooling in transit and getting them to your unit. It's a growing art, and a systematic change many places will have to undergo.

Dr. Adrianne Bischoff (30:40:000)

All right, let's go back to the case. The question everyone wants answered: what did the echo show? What's the diagnosis? Nim, you were correct — this baby had severe left ventricular systolic dysfunction, with an ejection fraction of 38%. For those less familiar with echo numbers—

Dr. Nim Goldshtrom (30:52:000)

That's all they're waiting for — show us the echo.

Dr. Adrianne Bischoff (30:55:030)

Normal would be more like 55–60% in a neonate. The baby had low cardiac output, with a left ventricular output of 65% [unit as stated by speaker; see Flags]. In cooling babies I frequently see relatively low left ventricular outputs, but not usually this low — maybe in the 90s is fairly normal, so 65 is probably lower than expected. The baby also had mild right ventricular dysfunction, but the left heart dysfunction was much more pronounced. There was an unobstructed aortic arch, no structural heart disease, all four pulmonary veins draining normally, and normal coronaries. At this point, on epinephrine at 0.05 mcg/kg/min and prostaglandin at 0.03 mcg/kg/min, there was a large PDA (patent ductus arteriosus) measuring 5 mm with bidirectional shunting.

So now that you have a diagnosis — how do we approach severe LV systolic dysfunction with low cardiac output in a baby on these medications?

Dr. Nim Goldshtrom (31:40:000)

Feed and grow — just kidding. To reiterate some of the points you raised with the echo and clinical picture: even with a description of pre- and postductal sats, congestion, and left-sided dysfunction, this kid was almost certainly going to desaturate during periods in the unit, and this would have looked a lot like PPHN — I might even have started nitric oxide. My caution in these cases is that whenever I see an X-ray in the story of a kid who was fine, fine, fine, and then very quickly fell apart shortly after being on mom's chest, my fear is always PPHN or congenital heart disease — and the diagnosis could potentially be obstructed veins.

If it's PPHN and my X-ray is unusual, I'm always hesitant to just try nitric first, because it could make things worse — so I run through the function algorithm: let's just support the heart until we can get an echo, because that's what I'm most afraid of. It's such a problem that two diseases can look so similar, and one therapy will fix one while making the other disastrously worse. Not everyone has immediate access to an echo, and this child had to move to another center to get one — sadly the fate for a lot of obstructed TAPVR cases born in centers with lower resources, who then have to be rapidly escalated before a diagnosis can be found. Everyone gets stuck: do you start nitric or not?

To that point, going back to the very first things — normal heart rate, narrow pulse pressure, normal blood pressure, high lactate — start something. That's shock by definition. Whether after that you're debating whether it's desaturation plus PPHN 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'd have done everything: epi and nitric, and waited for the echo. Now that you're seeing an open duct with bidirectional shunting and severe LV dysfunction — like the premature physiology — this will take time. Part of the reason is understanding why the kid went into shock, anatomically. You have no structural heart disease, which is great, normal veins, normal coronaries — no coarctation, unobstructed and non-hypoplastic arches. You don't have a Shone's-complex-like picture with small mitral valves and other small structures — this is really just a normal heart that's in shock. This will take time.

There's some literature on the right drug of choice — milrinone, dobutamine, and epinephrine. I'm not up to date on the most important studies about which has the best efficacy for heart recovery, but to some degree what's most important is that these three drugs offer different options: options for normotensive LV dysfunction, and options for hypotension with normal function. They let you choose — if I have hypotension, I need beta and alpha support, that's epi. If I have normal tension but function is really bad and I need to get the heart pumping quickly, that's dobutamine. If I have dysfunction with normal tension, possibly both LV and RV, milrinone could be helpful. That's the broad framework I use. How do you approach these drug classes, and is there evidence driving you toward one choice or another for these conditions?

Dr. Adrianne Bischoff (35:45:000)

Between dobutamine and epi, my practice is similar to yours — it depends on blood pressure and degree of dysfunction. For mild-to-moderate heart dysfunction, whether LV or RV, where blood pressure is normal or just slightly low, I think dobutamine is fine — it's a cleaner drug and causes less confusion, with less risk of hyperglycemia and elevated lactate that can sometimes come as a side effect of epinephrine, not necessarily related to the underlying heart dysfunction. For severe dysfunction or hypotensive babies, I tend to go with epi, just because you get more effect for the dose. I don't think either is wrong — if you only have one available or are more used to using one, that's fine.

I try not to use dobutamine much beyond 5–10 mcg/kg/min. If I get to 10 and I'm not seeing improvement in heart function or perfusion markers, I tend to switch to epi — again, more effect for the dose. Escalating dobutamine beyond 10 tends to just add chronotropy without much more improvement in cardiac output or stroke volume.

With epi, as I mentioned, it's also dose-dependent — if I'm using it for inotropy, I don't want to escalate beyond 0.1 mcg/kg/min, because I don't want to worsen things from an alpha-receptor standpoint.

I'll add a caveat on milrinone — this was my own project, so a bit of self-promotion here. We looked at babies with hypoxemic respiratory failure and pulmonary hypertension who received milrinone as an adjunct to nitric oxide, comparing cooled and non-cooled groups. In the cooled group — a very small sample — we had a lot of trouble using milrinone; some babies became severely hypotensive. We have to remember milrinone is renally excreted, and babies with HIE are more prone to acute kidney injury (AKI), and may also not be urinating due to SIADH (syndrome of inappropriate antidiuretic hormone secretion) and other factors. Therapeutic hypothermia also affects drug clearance. We saw a couple of patients with catastrophic hypotension — single-digit blood pressures — needing significant escalation of other vasopressors to recover. They all survived, but had worse outcomes and needed a higher inotropic score. So we're quite cautious about milrinone in cooling babies — we don't use it, out of that concern. Since publishing that, I know many centers do use it, and given the small sample size, it's very possible that effect was limited to babies with severe AKI or borderline blood pressure at the start. I don't have that level of nuance, but here at Iowa, we're fairly cautious about milrinone during therapeutic hypothermia — it's a drug we don't typically use during cooling. If I need inotropic support in a cooling baby with HIE, we go with dobutamine or epi during cooling, and reserve milrinone for after hypothermia has resolved.

Dr. Nim Goldshtrom (39:50:000)

What if they're hypotensive on either of those drugs — then what? Do you add a vasopressor on top, or keep escalating? What's your usual approach?

Dr. Nim Goldshtrom (40:23:618)

You bring up great points — there are pros and cons to milrinone. Continued hypotension suggests other parts of the system aren't working. The cardiovascular system is built around preload, contractility, and afterload, and you're addressing certain things with inotropes; volume and fluid shifts aren't typically the main issue, though some kids do need extra volume resuscitation. The assumption is that a child who's maybe mildly sedated and/or recovering from shock probably has vasoplegia — this isn't uncommon in kids presenting with various forms of distributive shock, or multi-compartment cardiogenic shock. This is exactly how kids present with severe shock after congenital heart surgery — volume and inotropes first, and when they're still hypotensive, we assume refractory vasoplegia and add a pressor. Vasopressin is a very common choice when we need more alpha effect, since escalating epi only gets you indirect alpha, not the direct alpha you'd get from another agent. You could also use a bit of norepinephrine and epi if needed, or go to stronger agents like phenylephrine if you really need more vasoconstriction.

If you continue to have hypotension despite imaging-guided evidence — echoes showing improving squeeze, better contractility than before on your current inotrope, and no signs the heart is under-filled or volume-responsive — meaning you're not on the preload-recruitable part of the cardiac output curve — the assumption has to be vasoplegia, and you should probably add a low-dose afterload-increasing agent like vasopressin or norepinephrine to help through this period until more of the inflammatory cascade resolves.

Dr. Adrianne Bischoff (42:13:592)

Can you educate us a bit more on blood pressure targets and autoregulation in this type of patient?

Dr. Nim Goldshtrom (42:20:000)

This is Keith Barrington's world — he's spent a career on this and still hasn't given us a perfect answer as to the ideal blood pressure target. But there are interesting, novel developments. Everyone was looking forward to the HIP (Management of Hypotension in Preterm Infants) trial, which had to stop early due to recruitment issues, but new technology is giving us some answers. In the mid-2010s, groups from Texas and Johns Hopkins were looking at autoregulation — a feature we can now use to guide what blood pressure looks like as the brain reacts to it. Jennifer Lee's group at Johns Hopkins looked at therapeutic hypothermia, using tools like NIRS devices alongside blood pressure to evaluate optimal blood pressure in this population going into cooling, during cooling, and after cooling, in relation to developmental outcomes.

The first interesting finding from these studies — which we'll link on the site — is that the optimal blood pressure for term neonates, with a gestational age hovering around 40 weeks in this prospective study, was around the low 50s — about 51, plus or minus. So compared to what many of us use — gestational age equals MAP — there hasn't been a great deviation from that rule; there's still no consensus on whether you target the 10th percentile or the 50th percentile for better outcomes. Most of us are trying to first do no harm and probably use the "GA equals MAP" rule as good enough.

What's fascinating — and there are preterm studies we'll also link — is that preterm infants in the first transitional period may not follow "GA equals MAP" either. In preterm infants between 24 and 28 weeks, the safe portion of the cerebral autoregulatory plateau is approximately 10 points above their gestational age during the transitional period. But there aren't yet studies suggesting that targeting or living at that number is associated with a different or improved outcome — it's just an association showing what the brain seems to want is actually higher than the typical 50th- or 10th-percentile targets. What's fascinating about Dr. Lee's study is that they saw a small association with MRI findings at two years of age — particularly, during the cooling and rewarming phases, more time spent above the lower limit of autoregulation (in the "optimal MAP" range) was associated with less white matter injury. Again, this wasn't an intervention — they just tracked where babies sat relative to their autoregulatory curve, and more time spent above the lower limit was, quote-unquote, "safer" for brain injury. These are fascinating studies about what the future could hold, and we certainly need more prospective research on whether targeting that blood pressure and driving toward that number makes a meaningful impact — and, importantly, whether doing so avoids causing other problems, like brain bleeds or further brain injury.

We do some of that in practice here — I've gently moved my own threshold slightly above gestational age, because if a baby's already on an inotrope recovering from heart disease, what's the marginal difference between a MAP of 40 and a MAP of 45 in a full-term kid? But I'm cautious that if I ask my group to target these higher numbers the autoregulation literature suggests, it could increase therapeutic creep without strong evidence. We have to be cautious about waiting for more studies that show real utility and value, like what already exists in adult traumatic brain injury research. I don't yet deviate much from "GA equals MAP," out of concern about adding therapeutic burden without strong evidence that I'm doing something more positive than simply targeting a reasonable MAP — and without knowing the child is truly gaining more benefit until we have more research.

Dr. Adrianne Bischoff (46:27:074)

Those are all great points. Along a similar line — how much do you want to fix the problem? We know from Dr. Giesinger's studies that RV dysfunction is associated with worse outcomes. But is RV dysfunction simply a marker of the severity of the hypoxic insult, meaning these babies are more likely to have worse outcomes regardless — or is it that if we fix heart function and improve cardiac output, we might actually improve white matter injury and brain outcomes too? And to what extent do you fix it — what's the optimal level, not just for blood pressure but for cardiac output? Because we also want to avoid reperfusion injury — we don't want to go from low cardiac output due to heart dysfunction and asphyxia straight to supranormal cardiac output that could worsen reperfusion injury itself. There's just so much we don't know, and I agree it's hard to implement changes based on vital-sign numbers without enough prospective and physiological studies to tease that apart.

Dr. Nim Goldshtrom (47:40:000)

That's one of the landscapes of the future — we all have nice new tools and data points that clearly add value above what we're currently doing, but integrating them and getting them into multicenter studies so we can power these questions and get answers faster is the challenge. Hemodynamics monitoring isn't available everywhere, and I'd guess the hemodynamics community still faces the challenge of coordinating a shared study this year, pooling data and patients to get numbers — not for IRB purposes, but just because collecting all of this is genuinely hard. That's what it will take — this kind of approach where every center contributes, say, 50 babies, and we get to 500, and we can answer the question, because that's the level of effort required. Autoregulation research is the same — only a few places have the technology, so you have to pool it. But this is what we should all be striving for: getting patients exposed to these new tools into shared databases and systems so we can get answers faster. This should be one of the promises of AI — helping us link massive datasets faster, getting answers from data that already exists but is separated by distance, time, and network infrastructure.

Dr. Adrianne Bischoff (48:48:246)

100%. So, back to our case — we have our asphyxiated baby with unexpected left heart dysfunction. I'd classify the core priorities in managing this baby as, first, supporting myocardial function — optimizing inotropy, which we said could be epi or dobutamine; personally I wouldn't use milrinone here, though that's debatable. Another core priority is myocardial oxygen demand — this baby is already cooling and intubated, but if the baby were extremely agitated or in pain for any reason, I'd want to address that too, since I don't want additional stress on this physiology.

In severe LV dysfunction where the RV isn't as impaired, there's a role for maintaining ductal patency, because functionally this works almost like a hypoplastic left heart — you actually want some right-to-left shunting to support the systemic circulation. I don't want this baby at 100% saturation, because at that point I might shift the ductal shunt toward more bidirectional or left-to-right flow and lose that supportive flow. I'd rather have a blue baby with flow than a pink baby with no flow, which ends up being a gray baby — I'd always rather have a blue baby than a gray baby.

Dr. Nim Goldshtrom (50:35:000)

Correct — truer words cannot be said. Blue is always better than gray.

Dr. Adrianne Bischoff (50:45:000)

Along the same lines, we want to balance pulmonary and systemic circulation through that PDA — promoting some degree of right-to-left shunting, which may mean higher PEEP, slightly higher CO2 targets, or even lower oxygen targets, depending on severity, until the LV starts recovering. We'll know that as the days go by — if the lactate keeps improving and the pre- and postductal saturation split narrows, that may be a clue the LV is recovering and the circulation is no longer as dependent on right-to-left flow. I'd manage this baby with sequential echoes to decide when to wean prostaglandin, and then wean or stop the epinephrine.

Dr. Nim Goldshtrom (51:45:000)

Great summary. The only thing I'd add to that rubric — support the heart, decrease demand, and remember a duct can be used for a lot of things, not just closed in a preemie or kept open in congenital heart disease — is that time can be your friend and your enemy. It's your friend when you keep reevaluating: this physiology will change and improve, and the ductal gradient will eventually disappear. Once your sats are pre- and postductal in the high 90s, you could get an echo, but you probably already know you don't need it urgently — and you may want to start moving toward closing the duct, since you've offloaded the LV and function is better. Use this dynamic picture and the clinical tools — heart rate, blood pressure, lactate, shock — to guide starting treatment. Imaging is great, but not everyone has access to it all the time, and there's a lot you can learn from clinically watching a child evolve, allowing you to say: now we're relying on the duct less, the shunt usage has diminished, maybe we're promoting too much pulmonary overcirculation, and it's time to let the duct close. Use time as your friend to both guide therapy and understand whether you're meeting your targets.

Dr. Adrianne Bischoff (53:20:000)

Absolutely — these are the kinds of babies that keep me up at night, but they're also the ones that push us to become better clinicians.

Dr. Nim Goldshtrom (53:30:000)

Correct — literally and figuratively, they keep us up at night.

Dr. Adrianne Bischoff (53:37:000

For the audience — if you enjoyed this discussion and this format, 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 (53:41:000)

Absolutely — thank you for joining us. We enjoyed it, and we hope you did too. We'll see you all next time for more real cases, real challenges, and real-time learning in neonatal hemodynamics. Take care.

Dr. Adrianne Bischoff (53:55:000)

Thank you.