Okay, I'm Stephanie Levine. I'm at UT Health San Antonio as well as the South Texas VA. And I'll be introducing our panel today. I'm going to start off with a review of the normal cardiopulmonary physiology in pregnancy. And we'll have Dr. Lisa Moores talking about venous thromboembolism in pregnancy, Dr. Deborah Levine talking about pulmonary hypertension in pregnancy, and then Dr. Nancy Collip talking about sleep disordered breathing in pregnancy. So what we're hoping to accomplish over this hour is to talk about the normal, remind people about the normal respiratory and cardiovascular physiology. We'll talk about the diagnosis and management of VTE, explain the management of pH in pregnancy, and then hear about sleep disorder, breathing, and in pregnancy. I have nothing to disclose. So when we talk about the whole concept of pregnancy and pulmonary and critical care issues, you can have unique pregnancy-related complications as shown on this slide. And these are pregnancy-specific, such as amniotic fluid embolism, tocolytic pulmonary edema, peripartum cardiomyopathy, the HELP syndrome, for example. You can also have conditions that are worsened during pregnancy, so preexisting conditions that are worsened. And those will include some of the topics we're talking about today, such as pulmonary hypertension and sleep disordered breathing. And then you can have conditions that the mother is at increased risk of developing during pregnancy. And examples there that we'll be touching on are venous thromboembolism and, again, sleep disordered breathing. So let's start with this case. You're beginning your morning walk up the five stories of stairs at the VA to get to our MICU. The 26-year-old medical student rotating on your service pulls you aside and says, I'm 16 weeks pregnant, and I'm feeling a little short of breath and fatigued. My husband says my sleep is restless, and I am snoring. Is all this normal? On exam, she's a febrile, respiratory rate of 14, heart rate of 90, blood pressure 110 over 68. She's gained about 14 pounds in the pregnancy thus far. Her lungs are clear. You hear a systolic ejection murmur, but a normal S1, S2. Barely gravid abdomen. And she has trace 1 plus bilateral edema. So let's use this case to discuss the normal cardiopulmonary physiology. So the upper respiratory tract in pregnancy, there is hyperemia and edema of the airway mucosa. You can have increased secretions, particularly in the third trimester, but throughout pregnancy. Nasal polyps can develop or increase in size and number. You can have an increased incidence of allergic rhinitis. And not that we're talking about critical care issues today, but this all makes intubation difficult, more difficult in pregnancy. These are primarily estrogen-mediated changes. Here is a spirogram in the pregnant and non-pregnant state. So non-pregnant on your left, pregnant on your right. And of course, as pregnancy progresses, there is an elevation of the diaphragm due to the enlarging uterus. The diaphragms do maintain their normal contour and function, partially due to changes in the thoracic wall. And what we do know about pulmonary function and spirometry is that there's a decrease in residual volume and functional residual capacity due to the enlarging uterus pressing up on the diaphragms. There is an increase in tidal volume. We'll talk about some of the reasons for that. Residual capacity stays about the same. And total lung capacity decreases, but just slightly. And most of this is due to an increase in inspiratory capacity in terms of maintaining your TLC. I'll show you a series of graphs, and we have on our x-axis weeks of gestation, on our y-axis percent change. And as pregnancy progresses, one can see that there's an increase in minute ventilation. Recall minute ventilation is tidal volume times respiratory rate. And this significant increase is primarily due to an increase in tidal volume, much less so than an increase in respiratory rate. And one can also see this happens early. You're starting to have these changes as early as 8 and 12 weeks of gestation. These are mostly progesterone-mediated changes, and it's an increase in both central and hypercapnic respiratory drive. As I mentioned, respiratory rate increases slightly, but is not the significant contributor to the increase in minute ventilation. In general, flow rates do not change. Airway resistance does not change. Lung compliance, and I'm speaking specifically about parenchymal lung compliance, does not change. But of course, total respiratory compliance decreases, again, due to the enlarging uterus. Diffusion stays about the same. It varies with blood volume slightly during pregnancy. What about gas exchange? So because of the minute ventilation increase that we already talked about, there is a mild compensated respiratory alkalosis. PCO2 runs about 28 to 32. Bicarbonate drops accordingly, about 18 to 21 milliquivalents per liter. And your pH is slightly alkalemic. Your PaO2 stays about the same. There may be a slight increase in your AA gradient. There is a significant increase both in oxygen consumption and CO2 production during pregnancy and especially at the time of delivery. How about the cardiovascular changes? Again, similar graphs. X-axis research gestation, Y-axis percent change. And here you can see that the cardiac output increases significantly. And here, this is really due to an increase in both stroke volume and heart rate. So equal contribution of both parameters that make up cardiac output. Systemic vascular resistance normally decreases, as does pulmonary vascular resistance. So you can see how this will come into play when you hear about pulmonary hypertension. Blood pressure, there's decreased systolic and diastolic slightly. And then near term, it's near normal. And we always think and remind ourselves about postural hypotension that can occur during pregnancy. And often it's best to resuscitate our patients in the critical care situation in the left lateral decubitus position with the goal of getting the uterus off the IVC and therefore helping your preload and venous return. Here's what happens with fluid physiology as pregnancy progresses. There's an increase in your red blood cell volume. But a much greater increase in your plasma volume. And that explains the normal dilutional anemia that's typical of pregnancy. Because of that, there's a drop in your oncotic pressures. And most of these changes are a combination of mineralocorticoid as well as estrogen and progesterone related changes. Just reminding people about the FDA drug classification for pregnancy, many drugs are still being classified in the old system shown on your left with A, no risk, and successively increased risk with X being known teratogenicity. But now new drugs on the market will be labeled as you see it on the right. And that started actually back in about 2014. But some old drugs have not yet been converted. So any new drug on the market will be labeled with a PLLR, but there'll be a conversion over a lot of years for older drugs. So getting back to our case, dyspnea in pregnancy affects two-thirds of pregnant women. And it occurs as early as the first trimester, so it's not purely mechanical as you would see towards the third trimester with the enlarged uterus. As we mentioned, mostly progesterone mediated changes inducing hyperventilation and changes in carbon dioxide sensitivity. And then we mentioned the dilutional anemia that's also contributing to the cessation of dyspnea. But what we don't want to miss as pulmonary clinicians is, is there really something pathological that we should be aware of, such as an undiagnosed stenotic cardiac lesion, such as a right to left shunt, such as pulmonary hypertension. So what do we tell our medical student here? We say, this appears to be all normal for this stage of pregnancy. So from this section, I think our take-home message is to try to be familiar with the normal physiology in pregnancy. Most pulmonary issues are managed similarly to that in the non-pregnant patient, but there are some important caveats that we'll try to mention to you today. And then just a reminder that all your management decisions should be collaborative with us, with intensivists, high-risk obstetrician, neonatologists, our OB anesthesiologists, as you get later in term, and our specialty nurses. So thank you for your attention. We thought we'd hold questions to the end of the session, if that's OK with everyone. Here are some references. And I'd just like to highlight a very nice two-part article that was recently published. The second part is still online in September of this year in CHESS, looking at lung disease and gender differences. And there is a section on pregnancy included in that article. OK, very good. So I'd next like to introduce our next speaker, Dr. Lisa Moores. Dr. Moores is a professor of medicine, and she's the Associate Dean for Assessment and Professional Development at the F. Edward Herbert School of Medicine, America's medical school. Thank you, Lisa. Thank you very much, Stephanie. I have no conflicts of interest to disclose. I won't read the objectives here. But I did want to highlight that looking at the session objectives, it's fairly broad. And given that the time that I have with you all, I thought I'd focus more in on the diagnosis of pulmonary embolism in pregnancy. I'm not going to cover prevention, although that is an important topic and not so much on the treatment side. And why am I doing that? Well, luckily for us, the absolute rate of pulmonary embolism in pregnancy remains low. However, it is the sixth leading cause of death, maternal death, in pregnancy worldwide. And in developed countries, it's the leading cause of death. Luckily for us, DVT is more common. But again, given the high mortality, PE is something that we don't want to miss. It is spread across all trimesters and an equal distribution between prepartum and postpartum. One thing to remember, and I'll focus on that in the next slide, is that when you are looking at DVT, it is much more common to be on the left. And it's much more common to see isolated pelvic DVT. So something we need to think about, because our routine imaging for DVT on ultrasound doesn't always include that. So when you think about this, pregnancy really involves all parts of Virchow's triad. And as I mentioned, the DVT is more common on the left. When you think about stasis, looking at the anatomy, the right iliac artery is crossing over the left iliac vein, and then you've got the gravid uterus now pressing on that. So that is why you see that left predominance. But there are other things causing stasis, not the least of which is women who have other comorbidities or complications of their pregnancy and have significant immobilization. Of course, we have the vascular or endothelial damage that comes along with just normal delivery, but can be heightened, of course, if a cesarean section is needed. And then we have a significant hypercoagulability state, both during pregnancy, but then, of course, during delivery, and even heightened again if surgical delivery is necessary. And the risk factors for venous thromboembolism in the pregnant woman are the same as those in the non-pregnant population. However, we then add several, as highlighted in blue here, that are specific to the pregnant patient. I wanted to focus on just a couple things here. One is that c-section is probably the greatest risk factor that is specifically related to pregnancy, but it's hard to sort that out. It doesn't appear to be that it's just the surgical procedure itself, but that women undergoing c-section often have significant either complications of pregnancy, such as preeclampsia, or other comorbidities that are adding to that increased risk. When you look at prior VTE, this is, of course, a risk for the non-pregnant population. In the pregnant population, this is stratified a little bit in that if their prior VTE was related to hormonal therapy, or occurred in the setting of a prior pregnancy, that's a significantly increased risk. And as with other patients, if it's an unprovoked prior event, that also increases their risk. For the thrombophilias, this is something that we could probably spend a lot of time on. And similar to the non-pregnant population, we know they're there. We know they increase incidence, but how they play into our decision-making is a little bit more complicated. But in the pregnant patient, the ones that worry us the most are going to be the homozygous variants, or some of the heterozygous variants. But predominantly for the heterozygous, that only comes into play if there's a significant either personal or family history of VTE. And the reason that I wanted to take my short time to focus on this is that diagnosing PE in pregnancy is difficult. Dr. Levine already took you through the significant physiologic changes, and how common it is to have dyspnea. And many of the symptoms that we think about with suspected pulmonary embolism are there in normal pregnancy. In addition, when we tried to look at our normal approach to diagnosing pulmonary embolism, pregnant patients were excluded from almost all of those trials. So we don't have any validated pretest probability tools. We suspect that the D-dimer is not going to be very helpful for us because we know that it rises in normal pregnancy with each trimester. And even if we trusted the D-dimer, we don't know how to interpret it because we don't have a good validated pretest probability tool. And then, of course, we would like to use those because we have concern for the radiation exposure for both mom and the fetus if we have to go to imaging. But I think it's important because the false positive rates put a significant risk for the mother and the baby for fatal bleeding at the time of delivery. So a little bit on those clinical decision rules. The one we probably, at least in North America, use most commonly is the Wells Rule for both DVT and PE. And these have not been validated in pregnant patients. There was a small retrospective study that suggests that it had a fairly high sensitivity using a cutoff of four or six, but it has not been used in any prospective management trials. Neither has the pulmonary embolism rule-out criteria or the PERC rule. When you talk to Dr. Klein, he really, every time he speaks of this rule, he cautions that it often fails in pregnant and postpartum patients and shouldn't be used in that population. There is a rule that is commonly used and has some degree of validation for DVT, and that's the left rule. But there really isn't a well-validated clinical decision rule for pretest probability for pulmonary embolism, although we may be making some progress there. There is one that was recently proposed. This is called the Pregnancy Adapted Geneva Score. And what these authors did was take a large, large series of women who went through normal pregnancy, some of whom did develop a venous thromboembolic event, and they tried to look at how well the Geneva tool did and whether they could adapt it. As you can imagine, if they look at that cohort, there really weren't any women that were over age 65, so they thought, all right, we could just delete that. But then they took a step back and said, well, maybe there's a different cutoff that we could use. So they looked at a receiver operating curve for age in that pregnant population and were able to find the cutoff of 40 had a significant discriminatory value, similar to what the age greater than 65 does in non-pregnant patients. So they included that with the same point score as the greater than 65 in the non-pregnant. In some of these dichotomous variables, they just left them as is, although they also excluded an active malignant condition because that was so rare in pregnant women. And then the only other variable that they looked at was the heart rate. The heart rate in the normal Geneva score of 75 to 94 did not work well in the pregnant women. But again, looking at a new ROC curve, they were able to find a cutoff of greater than 110. So this is their proposed revised score for pulmonary embolism in pregnancy. And it had a decent discriminatory power in this group. But again, this was a sort of a derivation and an internal validation cohort. This score has not been used in any prospective management trials yet in pregnant women. And then I mentioned the D-dimer. D-dimer actually works well in pregnant women. Yes, the levels rise. But if you have a negative D-dimer, it is as useful as in the non-pregnant population. The sensitivity is high, the negative predictive value is high. But of course, again, we worry about the diagnostic utility of it because we don't often see a normal D-dimer. So there's a lot in the literature about saying, can we come up with different cutoffs for pregnant women and increase that specificity or diagnostic utility without affecting the sensitivity? And you'll see several out there. Some have suggested raising the threshold 50% in the first, 100% in the second, and 125% in the third. But what we do know is that the low pretest probability in a normal D-dimer, using that left rule, can exclude DVT. So the real question is, if we can find the right cutoff perhaps or the right way to use the D-dimer, can we use that same approach in pregnant patients? And if so, what clinical decision rule are we going to use? And until about four years ago, we really didn't know the answer to that. But we do have two pretty well-done prospective management trials. The first was the CTPE pregnancy trial, and this was published in the Annals in 2018. This was a multi-center prospective management trial, about 11 centers in France and Switzerland. And what they chose to do was to look at pregnant women with suspected pulmonary embolism, and at that time they used the revised Geneva score, and by revised I mean the one we used in all patients, not this pregnancy adapted, which had not been proposed at the time of this trial design. And using this, even though again it had not necessarily been validated in pregnant patients, they used it similarly to what you would do in non-pregnant patients, with one caveat being that pregnant women who needed imaging, either because they had an abnormal D-dimer or a high pre-test probability using the revised Geneva score, all went to compression ultrasound as the first imaging, regardless of whether they had any symptoms of DVT. If that was positive, of course, they made a diagnosis, and then if that was not helpful, then they went on to imaging, and their study of choice was the CT angiography, and they only went to VQ if the CT was indeterminate. And these are the outcomes in terms of, their primary outcome was twofold, one was looking at the diagnostic utility of this algorithm, the other was looking at what we do in all PE trials, and that is, what was the rate of subsequent venous thromboembolism in the three months following if they excluded pulmonary embolism and did not treat patients based on this algorithm? And you can see in terms of PE being diagnosed, most of this was done via imaging. In a small number of patients, 11% of them, they did have a negative D-dimer, and an appropriately low pretest probability that they were able to exclude pulmonary embolism, but you can see the majority of patients had to go to imaging in this trial. What they could say is this algorithm was safe. They only had one or two patients, I can't recall the exact number, but a very low number, similar to what we see in non-pregnant trials using non-invasive approaches to the diagnosis of pulmonary embolism. Again, but the number in whom they could exclude was relatively small, and the diagnostic yield of compression ultrasound was very low, which again, probably, if we can avoid the radiation, still may be useful, but I think we need to think about the efficiency, particularly the cost-effectiveness. I think the second trial was a little more intriguing. This was published a year later, and this was the Artemis trial using the recently-validated YEARS algorithm for suspected pulmonary embolism and applying that to a pregnant population. They had about 500 patients, and they ordered a D-dimer, and then they applied the YEARS criteria, which for those of you who follow this, this is clinical signs of deep vein thrombosis, the presence of hemoptysis, and then similar to the Wells rule, there's a subjective component of pulmonary embolism as the most likely diagnosis. So that is the YEARS criteria, and it's divided into whether you have none, which is a low risk, or you have any of them, which is considered then intermediate or high or non-low risk. In this algorithm, one of the differences was, as you see, they did not do compression ultrasound unless there were signs or symptoms of DVT, and if they were present, they started there. Otherwise, they looked at whether the YEARS criteria were present, and then they had a sort of a two-level, so a risk-adapted cutoff of D-dimer at 1,000 if the risk was low, and at 500 if the risk was higher. And you can see in this study, interestingly, there was a significant proportion of women in whom they were able to exclude pulmonary embolism without going on to diagnostic imaging. There were some women in both arms who did have subsequent imaging, which broke protocol, and they explained why that was done, and there was only one patient who had a subsequent VTE event, and that was a DVT in follow-up. So they had a very low rate. This is, again, very consistent with our non-pregnant trials, and even if you assume that all the patients that were lost to follow-up had a PE, that rate would have been, again, very low. And I think the nice thing about this trial is almost 40% of the cohort was able to have PE excluded without any chest diagnostic imaging. And the safety was similar among all three trimesters, but another nice caveat to this trial was that we were able to avoid diagnostic imaging in 65% of patients in the first trimester, which makes sense. The D-dimer's gonna more likely be low in that first trimester, but that's when the radiation is likely most harmful to the fetus. So I think this was a really helpful trial. I wanted to just take a moment and talk a little bit about that chest imaging. There is a lot of debate between VQ and CT. They've never been compared head-to-head in a management trial of pregnant women, but there are several meta-analyses. This is one of the most recent. And they're both accurate. They both involve some degree of radiation. But the upper limit of the dose that the fetus would see is a threshold way below the teratogenetic threshold. So some of the other issues that come into play are really what is the maternal radiation, particularly to lung and breast tissue. The exposure during CT is higher than in VQ, can be somewhat limited with the bismuth breast shields. So I think some of the quandary that we run into is really the fetus is probably gonna be okay. CT might be a little bit riskier for the pregnant woman, but some of that might also depend on whether the chest X-ray is normal and whether we feel we're gonna get a diagnostic VQ scan, the availability of VQ. And I think, interestingly, whether we can optimize the CT algorithm in pregnant women. This again is another nice recent review looking at CT versus VQ. And you can see that a lot of concern in the past has been that there's gonna be more non-diagnostic VQ scans. But actually the non-diagnostic rate is similar and that's because of, again, the changes that Stephanie mentioned in the circulating blood volume changes the women's physiology to where there are often non-diagnostic CT scans because you don't get adequate opacification of the pulmonary vascular tree. So really the non-diagnostic rate is about the same, but it's going down in both. The radiation concern also appears to be going down with newer CT algorithms with lower dose. And some of the studies suggest that the risk of breast cancer is not significantly elevated, but the time of follow-up is still short. So I don't think we've answered that question, but there is a nice recruiting trial going on right now trying to optimize, and it's called the Optica trial, trying to optimize that CT algorithm in pregnant women so that the non-diagnostic rate goes down, the amount of IV contrast being used is lower, and the radiation is lower. So I think if we can optimize this, perhaps the study of choice may swing more towards CT given the lower risk to the fetus and the fact that we can look for alternative diagnoses. And I think one point I would wanna make is that we shouldn't be afraid of imaging if we need it because the mortality of PE is much higher than any potential teratogenicity or carcinogenesis. So in summary, I think when you look at current guidelines, and there was a nice review of these in CHESS just a few months ago, they're all over the place. They're very conflicting, not just in diagnosis, but in who we should give prophylactic treatment to, how we should treat this, how long we should treat it. But we, at least in the field of diagnosis, now have some pretty good studies, and I really think the time is right to update guidelines in this area. So hopefully these will be coming in the near future. So I will turn the podium back over, and happy to answer questions at the end. Thank you. Thank you Thank you All right. Now we are going to move on to our talk on pulmonary hypertension and Doctor oops Okay, great, dr. Debbie Levine and is presenting and she's a professor of medicine at Stanford University Thanks Thanks everybody and thanks for inviting me to give this talk and I think again with the short time I decided that we'll talk about pH and delivery because we only have that much time but So no, so we're gonna start off with it, can you guys hear me by any chance? Okay, and we're gonna start off with the case and this is a 22 year old female G1 p 0 32 and 4 7 weeks pregnant who came to an outside ED actually with two days Two days ago with progressive dyspnea dizziness ankle swelling. She's had no prenatal care In fact, she was coming from over the border and had been told as a youngster that she had a quote-unquote heart disorder Or condition on physical exam. She was mildly hypertensive She was tachycardic and breathing 30 times a minute and she was only 86% on room air. She was dysmic loud p2 and also had a 2 plus edema and That is the same thing I just showed you So this was her echo and you can see they did an echo while she was in the ER you can I'm sure where the pointer is but very large right heart and kind of delving into the The left ventricle and she basically had not she had an echo as a youngster She said but basically didn't know what it said She underwent right heart cath at the other hospital and she had a PA pressure of 94 over 40 with the mean of 59 her pulmonary capillary wedge pressure was 7 and her PVR was eight point four woods units So if you're using and I'm sure you've heard over the last couple days that there are now a couple of different definitions of pulmonary hypertension and either way you do it with the woods units of two or you woods units of three we definitely have made the grade of pH so pulmonary hypertension is a Deadly disease a fatal disease if not treated and even when treated it's a progressive vasculopathy of the small pulmonary arteries as the as the as the Vasculopathy worsens and the lumen of the pulmonary arteries get smaller the pulmonary vascular resistance will go up the cardiac output will Go down and that's mostly what patients die of is right right heart failure and right heart dysfunction Remember when the PVR goes up it's kind of fixed It's not going to open up as we'll see in what you need for for pregnancy as dr Levine had kind of showed us in pregnancy Remember in normal pregnancy you have an increased cardiac output and an increased volume status and in a normal pregnancy Your vasodilation that we talked about a few lectures ago basically Accommodates for that and patients can deal with that increase both the volume and cardiac output In patients unfortunately with PAH those those arteries are constricted And they're not going to open up and so you're working against a fixed Pulmonary artery bless you without the ability to vasodilate so these patients Unable to accommodate that have worsening right heart dysfunction and have problems throughout the delivery and and afterwards The issue sometimes is when many of the patients don't have a problem during pregnancy It's pretty much After during delivery and after and so people get a kind of a false sense of hey things are going great for us So I think that's something to keep in mind is that the most sensitive time for these patients is usually within the first week post Transplant, but volume status can't equilibrate until about 20 and completely until about 20 weeks after so you really have to Know that you're you might be you know free and easy during the pregnancy, but after you you may have some issues Okay, sorry I Will learn the right way to do it So there's many studies, and I only showed two because we don't have much time But I was just trying to show kind of the outcomes over time because way back when when this study was done They looked this is from 2009 and they looked at two different eras earliest era being 78 to 96 and the later era being 97 to 2007 and you can see that basically back in back in 2000 back in 1978 about 56 about a 56 percent of patients weren't able to survive and so I think This number has been there forever, and this is what we worry about When you look another decade after that you can see that it looks like the numbers have been improved One of the things we have to look at when we're looking at any of these studies, and there's many single centers trials There's registries. There's you know multi-center trials look not trials But registries looking at this and we have to always remember What are they calling pulmonary hypertension? Some of the earlier studies have a mixture between people who are diagnosed with right heart cap and people who are only diagnosed with echo So we're not sure if they were pah ph. You know sec group 2 group 3 We we are not really sure, but we do know that it looks like things got a little bit better There's a study called the Ropak study registry of pregnancy and and cardio cardiac Disease and that was done. I think up until 2018 and what they found they had 5,000 over 5,000 patients at all cardiac diseases and They looked at you know survival and successful pregnancy what they called successful pregnancy Were patients who had a normal life afterwards and their their their baby was okay as well So really there were 40 patients in that study that were deemed as pah And they had the highest mortality of all the other five five thousand patients. I think all comers it was 0.6 percent that died and The pah patients had 10% way better than this 56% we see here But still pretty high and this is the more more recent study It's a single center trial looking at 83 pregnancies in 72 people and it showed that basically there was a 14 percent maternal death But then you look also don't forget that you also have patients with heart failure And I'm not sure what happened to all those so when you when you look at really morbidity and mortality We need to can consider looking at that so it looks like with all of our new medications and our Multidisciplinary care and all the things that we have that we're doing much better But I think as they should all of the guidelines still advise against pregnancy and advise us as clinicians to still advise against pregnancy at this point and This is even including the brand new guidelines from the ESE or s from 2022 just out a couple months ago It shows us that hey When you're talking to your patients, which you should the very first time you see them and meet them in their childbearing eggs against Pregnancy it should be including advice against becoming pregnant now I don't know what everyone else thinks about how the wording is of this document versus others But to me, it seems a little bit softer and maybe we can talk about it after they still advise against it but for some reason it's just a little bit softer of a only Guideline, but I think it's still definitely when you see a patient in clinic advise them against doing getting pregnant So Unfortunately, even though we have these guidelines and we know what we would like to do There's still occasionally PAH is diagnosed during pregnancy or PAH patient becomes pregnant You know as the drugs get better patients feel better. They feel more active and they don't see sexual activity as a limitation or they don't see their PAH as a Limitation to sexual activity and things happen and you will see patients With who are pregnant and when you do I think you know, we've done a really good job with education We've done a good job with centers of excellence really understanding what you do with this set of patients These are the patients that are already pregnant. We really, you know can't do much they're pregnant So we have to take care of them one way or the other Whether they go through medical termination or they go through pregnancy. We still are taking care of them prevention It's that was you know, a couple steps back But when you have a pet a patient with the pregnant patient with PAH, I think you know We see them we look at what their risk factors are There's definitely poor prognostic features that we can assess their risk and kind of then go down to this Counseling with them with high-risk OB and really discuss what the Options are for them at that point if the patient decides, you know, I'm I'm really ready to take on that I want to have this child Or I want to go through this pregnancy then you start the clock ticking looking at building a extensive multidisciplinary team to work on Both the evaluation the care the monitoring and Decisions that have to be made difficult decisions, but I want to tell you one thing as well I didn't put this slide in because I didn't think I had time But I think we also have to know what right here is even for patients who don't elect to continue their pregnancy when patients go through medical termination or Depending, you know depending on when it is You still have to do these same steps These patients are still at risk if you have a you know Later medical termination if that's what they need or even in even earlier So I think no matter what these things are important to continue to consider with your team Okay, I'm just gonna use this one so I'm not even gonna look at that little button. But anyway, so now we're gonna talk about what we're really here to talk about And that's important decisions made with the multidisciplinary team During delivery and the delivery has really multiple multiple parts to it the decisions that have to be made are really split up into How are we going to deliver her? When are we going to deliver her and and really who's who should be there? so when you talk about The the type of delivery you can do delivery versus vaginal delivery versus c-section, you know Whenever I look at this talk for the past few years I've you know in the literature really kind of focuses on benefits of Cesarean section and most studies show that that's what they are. It's more controlled, it's planned, it avoids the prolonged labor. And really, in the last year or so, it looks like, you know, the decision has to be... The guidelines are talking about decisions have to be made on that particular individual. So every case is a new case. So don't make a blanket statement about, you know, delivery versus cesarean. It's how your multidisciplinary team is going to go over that. I think, still, the majority of patients are delivered through a C-section. So I think there's risks and benefits of both, but this has to be discussed with your multidisciplinary team, which includes high-risk OB, which includes cardiothoracic surgery and ECMO, pulmonary cardiology, RT. It includes a large team of people that all have their own thoughts, and that's the way that these people have to be managed during this sensitive time. What about the delivery? Well, I'm going to say I've never had one that went when we said it was going to go. We have these great meetings with all these people in the room. They're going to deliver the patient this way this night, with this person doing this and this person doing that. And the patient comes on Christmas Day when nobody's here. And it happens like that. That's why you have to have a contingency plan, and not just for you, but for every single member of that team. So if the OB-GYN is someone who is going to be there and she or he is not there, who is going to take that place? What about the cardiac anesthesiologist? They all are important members, so make sure that everybody has their own backup. When you're looking at a planned delivery, 34 weeks seems about what the experts are saying, if it's planned. And also if the mom and baby are, or the fetus, are stable. It often happens much earlier, whether planned or unplanned, and delivery has to happen sooner when the baby wants to come. Be ready for that, and have your team ready for that. In terms of who's going to be there, we already talked about who should be at the multidisciplinary team meetings, and if they're not there, who can fill in for them. These things are important when you're going through, what drips do we want, what medications can we use, can we use this OB medication, can we use that presser? Those are things that are really important. What about monitoring and management intraoperatively? There's many things here, but I would go over time, so I picked two of our favorites, hemodynamic monitoring in anesthesia and induction. But we can always ask questions after the others. So intraoperative hemodynamic monitoring, it's changed over many, many years. And when we first started hearing about this, and in papers that are old, they did have patients having a PA catheter in the OR, or even post-op, kind of measuring and monitoring patients throughout the delivery, and after their peripartum and postpartum time there. But really, there's very few times it's actually needed. And if your team is comfortable with it, then oftentimes the CVP monitor and A-line, as well as pulse ox and serial echocardiograms, or if the patient had to be intubated, even a TEE if needed. But really, the CVP catheter, I'm not sure how many people in the room use a PA catheter for these patients. You still do. And I think it's up to the comfort of what you feel the most experienced with and what will make you and your team feel the strongest about what's going on. So I think, again, up to the team, up to each member of the team. But again, things seem to have changed a little bit over the last 10 or 15 years. What about anesthesia? This slide last night was so full. I had, like, every line. So I took out a lot of stuff, but we still talk about it. It just looked too full. But really, the reason there were so many lines was because there's no evidence-based recommendations between regional, general, or combined. We know what's probably best, but we still don't have direct guidelines. We have recommendations. And again, I think it's patient-related. But most of the PAH guidelines do recommend regional anesthesia over general. And that's because the induction of a patient with PAH can be very difficult, challenging, and very fatal. Or not very fatal, fatal. And I think that the idea of using a regional has taken on what is usually happening, unless there's something. I did have to tell you, I did have a patient that nobody knew she had some really bad back injury and had surgery, and she didn't happen to tell us. They spent over, I don't know, three hours trying to get in an epidural. And it was ridiculous. There were so many people there. We just finally did it the other way. And it worked out okay, but it was kind of scary. But there are going to be times that you can't. Nobody could get into this space. So one of the things about regional anesthesia is that we want to always avoid single-dose spinal anesthesia. And that's because it can make the patient super hypertensive, and really, right now, what people are using and what we've used is more of a combined spinal epidural that's kind of dripped in slowly with incremental dosing rather than just one. The hypotension you can get from that single dose can be irreversible, and it can be detrimental, and we've seen it. So I think we've changed to mostly spinal epidural if possible with the anesthesiologist in agreement, of course. These are the things you have with that multidisciplinary team. Every step of the way has to be kind of looked at. If general anesthesia is required for some reason, think about what you're going to be using for both sedation and for pain. You know, during the operation, the pain management is probably better because it does have a little less problems with hemodynamics, but again, post-op, we're going to talk about those opioids. So continue to look at these anesthetic type issues and make sure that both the OB anesthesiologist as well as the CT anesthesiologist is available and happy with what you're doing. Got to go. Okay, last part, peripartum management. And basically, these patients go to the ICU. They should stay in the ICU, I usually think a week. I love 10 days, but no one ever gives us that. But remember, the first 72 hours are the most sensitive, but there's things that can happen and have happened after 72 hours. Close monitoring with CVP catheters. Meticulous Is and Os. You don't want, if you have your CVP catheter and you watch it, you don't want it over 5 to 7. You want it to be, because in that 72 hours, you're going to get that increase of fluid from all of the fluid shifts, and your CVP can go up and your right heart can have some dysfunction. Again, robust pain management. You need that. You don't want pain that can cause problems with the right heart. But remember, what also causes problems with the right heart? If you get constipated from opioids and you have to bear down, so watch for that. Adjust baseline PAH regimens as you can, and watch for all of the monitoring. Our patient went to C-section with a BTL. She was in the operating room with a CT operating with ECMO on standby. They're also part of your team. Who was there? CT, OB, pulmonary OB, neonatal, CT surgery, CARDs, and ECMO team were all there. She was put on epiprostanol at 22 nanograms per kilo per minute, as well as inhaled NO, slow infusion of the spinal epidural. She had a CVP catheter, as well as an ART line, as well as a Foley catheter. So management in the ICU for nine days, transitioned to IV triprostanol, which is a little longer acting, and had close hemodynamic and fluid monitoring for days, and then serial echocardiograms. So thank you very much. And you could read the summary, but I think I'm over time. So maybe some questions after. Thank you so much. Bye. Okay, so now our last speaker of the session is Dr. Nancy Collip. Dr. Collip is a professor of medicine at Emory University, and she'll be talking about sleep disorder, breathing, and pregnancy. All right. Okay. So I just want to thank Stephanie for inviting me, and it's a pleasure to be up here with the Drs. Levine and Mors, some of my favorite people in the world. So there's me. Here's our learning objectives. I'm just going to kind of roll here. So in the pregnant patient, there is a risk for sleep disorder, breathing. The prevalence is thought to be about 10% in the first trimester and increases over time, maybe as high as 25% by the third trimester. Part of what is challenging is about 30% of women enter pregnancy overweight or obese. That puts them at risk for sleep disorder, breathing. And about a third of patients that start normal weight will have excessive gestational weight gain as well. All those things put them at a higher risk. And the prevalence of snoring, as in Stephanie's case, she was snoring, is as high as about a third of patients. There's two-fold higher risk of gestational hypertension in pregnant patients that snore regularly, and they also have higher AHIs. One of the best studies that we had that looked at prevalence was the New Mom-to-Be study. They enrolled over 3,700 pregnant women and did home sleep testing on them, and they found in early pregnancy, about 3.5% had sleep disorder, breathing, and it almost increased two-fold by mid-pregnancy. We already kind of reviewed the respiratory changes that occur during pregnancy. Those that might impact sleep disorder breathing risk include that role of progesterone and the increased maternal metabolic rate with small drops maybe in oxygen saturation by the third trimester. And of course, as Stephanie mentioned, the upper airway, there's hyperemia and edema, including the nasopharynx and oropharynx, and even fat deposition around the neck may play a role. It's kind of redundant there. So sleep changes can also occur during pregnancy that may affect the risk of sleep disorder breathing. There's increased sleep fragmentation just related to being pregnant. Those of you who've been pregnant will know that. And also, nocturia obviously increases as pregnancy goes on. There's reduced sleep efficiency, duration, and quality. REM sleep actually goes down with a, not surprisingly, more N1 or non-REM level one sleep. And then they can also develop other sleep disorders like restless leg syndrome. So things that seem to increase risk for sleep disorder breathing, that rhinitis, the change in ventilatory drive, displacement of the diaphragm, altered pleural pressure, and early bronchial collapse and airflow limitation. Things that actually make pregnancy a little less risk is that lack of REM sleep, which we know sleep disorder breathing tends to get worse in REM, and they tend to spend less in a supine position. So some potential adverse outcomes of sleep disorder breathing in pregnancy would include, on the maternal side, gestational diabetes, hypertension, preeclampsia, and eclampsia. And for the offspring, depending on the study you looked at, there may be preterm low or high birth weight, intrauterine growth restriction, and admission to the neonatal ICU. And again, these are thought to be some of the pathophysiology for how sleep disorder breathing can result in an adverse pregnancy outcome, having to relate it to the oxidative stress and inflammation, increased sympathetic activity, impaired insulin and glucose metabolism with activation of the HPA axis, potentially leading to gestational diabetes and even hypertensive disorders. With regards, probably some of the best literature that we have is in relationship to gestational hypertension. They are the most common complication of pregnancy, and there's categories of chronic hypertension, development of hypertension during pregnancy, and then preeclampsia, which is new-onset hypertension and proteinuria. Usually in pregnancy, the blood pressure will rise a little bit and then fall back down to normal at term. And sleep disorder breathing, as we know in general, is thought to cause hypertension because of the intermittent hypoxemia that occurs. And obviously pregnant women would be at risk for that as well. And so two studies that looked at the relationship between gestational hypertension and sleep disorder breathing, they looked at patients that had gestational hypertension compared to controls in the first trial, and the gestational hypertension patients had reduced total sleep time, sleep efficiency and lower REM, and higher AHIs. Not particularly high, but still higher. And the odds ratio for having sleep apnea was quite high in the gestational hypertension patients. And another one where they did type three home sleep apnea testing at six to 15 weeks, and again at 22 to 31 weeks, again found a 7.1% incidence of sleep disorder breathing in those with gestational hypertension, lower in those with severe mild preeclampsia. With regards to the association of sleep disorder breathing and gestational diabetes, again similar in pregnant versus non-pregnant, it's thought that diabetes is thought to be increased prevalence in sleep apnea because of sympathetic surges, inflammation, and that oxidative stress, again due to intermittent hypoxemia. In a study where they came in to do home sleep apnea testing, inpatients that had gestational diabetes, 43% had mild sleep apnea and 63% had moderate to severe. So clearly some relationship there. We don't have really good data on the effect of treatment of sleep apnea on gestational diabetes, however. And then what about the effect of having sleep disorder breathing on the outcome of pregnancy? The studies are kind of all over the place. There's not very good prospective studies or they're typically a very small size and often don't adjust for confounders. The larger cohort studies suggest that there may be lower birth weight and more preterm births, lower APGARs, more C-sections, and higher neonatal admissions. One study out of Australia had 519, so a very small proportion of patients that were diagnosed with sleep apnea, less than 1%. They were diagnosed in the year before or during the pregnancy. And in this particular study, they found that the presence of the sleep disorder breathing did result in more gestational hypertension, preterm birth, lower APGARs, neonatal admission, and larger growth in age for infants. And this was in conflict to the other ones that showed smaller growth sizes. This was a meta-analysis that looked at different sleep outcomes on pregnancy and just highlight that it looks like in the meta-analysis, preeclampsia, gestational hypertension, gestational diabetes, and more C-sections occurred in those populations. And again, they looked at both subjective sleep disorder breathing and diagnostic obstructive sleep apnea, more preterm birth, small for gestational age. Actually, that was not significant, nor was the larger for gestational age. But low birth weight was also at increased risk for those patients. Possible risk factors for having sleep apnea during pregnancy is increasing age, presence of hypertension or developing hypertension, having diabetes, prior history of preeclampsia, twin gestation, and active and passive smoking. There's not great validated screening tools for sleep disorder breathing during pregnancy. Some have tried to co-opt other things like the StopBang and the Berlin, but as I'll show you in a second, they don't really make a lot of sense sometimes to be used during pregnancy. So the StopBang, of course, for those of you who aren't familiar with it, it's a way to predict the likelihood of having sleep apnea. Well, first of all, BMI is a problem, and most women who are pregnant are not over 50, and neither are they male, so not particularly good one to reference. And then with the Berlin, how often are you fatigued during pregnancy? How often do you feel tired? And, of course, the BMI there as well. So this study looked at these screening tools and one other one that had been proposed by FACO that looked at snoring, hypertension, age, and BMI. So they looked at some different screening tools to see during pregnancy how well they predicted. And, again, they had first trimester sleep studies in some, and then some also had a third trimester sleep study. And the actual best predictor was if in the first trimester, patients had elevated BMI, older age, and an enlarged tongue size. And that seemed to be the best predictor. But this hasn't been prospectively validated. Just to move on real quick through treatment, obviously when a pregnant woman has sleep apnea, can't really do surgery, and putting them on a mandibular advancing device or oral appliance is not really feasible because it takes a while to get those done. And so CPAP is usually what we turn to. Auto titrating may have an advantage during pregnancy because of increasing needs that may occur. They've shown that there's about a two centimeter increase in the pressure requirement over time. And most people, most pregnant patients, tolerate it pretty well. There's one small study that I show here that showed it may actually help with blood pressure control. But again, no good prospective studies. So to finish up, I'm almost done, but I have this really interesting case. This was a 36 year old that I saw that had severe sleep apnea. He was already on CPAP and was pregnant. And at the time of the blue arrow was when she had her child. And you can see the sleep got quite a bit worse right after that. And then you can also see, for those of you who look at downloads, this is what happened to her sleep. So you can see when the baby was delivered there, her sleep was pretty good prior to that. But then afterwards, it's like she's just trying to catch sleep whenever she can. But the other thing is we can look at, she was on AutoPAP and we could look at her pressure settings. And at her first trimester, her 90 percentile pressure on the AutoPAP was 9.9. It went up a bit again at the second trimester and then stayed about the same for the third trimester and then dropped back down in the postpartum. So I think it was a really cool kind of representation of that. And then the other thing that happened was you can look at flow limitation and snoring. And after her baby was delivered, that also improved. So in conclusion, breathing and sleep change during pregnancy and increased risk for sleep disorder breathing, particularly in those higher risk patients. So think about in your older, your obese, and your hypertensive pregnant patients. Untreated sleep apnea may result in adverse outcomes. So it's always advised to treat during pregnancy. Our current screening tools are not that great for those in use in the non-pregnant individuals versus pregnant. So we might think of newer tools to help to screen, but it's not really consistently done in most OB clinics. And that BMI age and tongue size, at least in that one study, would seem to be the best predictors, and stick with APAP. Thank you. ♪

Sleep disordered breathing

Sleep apnea

Pregnancy

Prevalence

Risk factors

Snoring

Adverse outcomes

Maternal risks

Baby risks

Continuous positive airway pressure