Hello, my name is Arthur Jason Vaught, and I am a Maternal Fetal Medicine Specialist and Surgical Critical Care Doctor at the Johns Hopkins University, and today I will be talking to you about COVID-19 and critical care considerations in pregnancy. First and foremost, I have no disclosures. The objectives of this talk will be to discuss critical illness as it relates to COVID-19 and pregnancy. During this discussion, we will discuss maintenance of normal pregnancy physiology and critical illness. We will also discuss ICU strategies in COVID-19 and pregnancy, and we will also discuss delivery timing and coordination of care with the ICU and MFM team. So the first thing that we have to ask ourselves is, what is normal pregnancy physiology? So to state briefly, pregnancy is a hyperdynamic cardiovascular state superimposed on a respiratory alkalosis. If you can follow my pointer, when you look at the cardiac output, it increases from eight weeks pregnant to 16 to 24, and then peaks right at about 32 to 34 weeks. We further see that this cardiac output is augmented by labor. So let's digest what's happening here. So the heart rate increases by 10 to 15 beats above the resting heart rate throughout pregnancy, and the stroke volume or the intravascular volume in pregnancy increases by 40% to 50%. This is causing the increase in cardiac output that we're seeing here. What we're also seeing is that we're seeing a decrease in the systemic vascular resistance. This decrease in systemic vascular resistance further augments the cardiac output, which helps perfuse the fetus and placenta. When we look at the respiratory physiology, we've already mentioned that pregnancy in itself is a respiratory alkalosis, and here's how it does it. We can see the tidal volume in the non-pregnant state and the tidal volume in the late-pregnant state. As you can see, there is an increase in that tidal volume. However, we see a decrease in respiratory volume, a decrease, excuse me, in reserve volume and a subsequent decrease in functional residual capacity. When we put these pulmonary changes in the clinical context, we can see that, again, that there is a respiratory alkalosis. The pH is 7.4 to 7.45, and the PCO2 drops from a normal of 40 to 27 to 32 milliliters of mercury, causing the bicarbonate to drop to 18 to 21 from 24 milliequivalents per liter. Also within this context, it's important to note that pregnancy itself is always a difficult airway. There can be difficulty masking the pregnant woman. There's also gastric dysmotility, placing the patient at higher risk for aspiration. There can be rapid onset of hypoxemia after induction secondary to this already discussed decreased functional residual capacity and difficulty in searching the laryngoscope, leading to poorer views and increased risk of bleeding. So these are really not great changes for someone who gets a COVID-19 or pulmonary infection, especially if they get subsequent ARDS. So why have these pulmonary physiology if it really sets you up for failure from a pulmonary standpoint? Well, these changes help maintain fetal physiology, and fetal physiology is reliant on the bicarbonate gradient made by the respiratory alkalosis. If you recall, we already said that the bicarbonate falls from a normal level of 24 milliequivalents to liter to 18 milliequivalents a liter. Also the higher cardiac output and lower SVR is thought to perfuse the placenta and thus the fetus. However, it's really important to note that a lot of this is theorized. And when we think of theory and we think of the maternal physiology and the fetal physiology, we have to think about within the setting of COVID-19 and acute respiratory distress syndrome, how do our critical care maneuvers alter the maternal and fetal physiology? And I'm specifically talking about lung protective ventilation for ARDS and furosemide or diuresis for dry lungs. When we think of COVID-19, it's easy to think of it within three stages. The first stage being early infection, which is mainly mild constitutional symptoms such as fever and dry cough and lymphopenia. Stage two being a pulmonary phase, which is most likely clinically seen with shortness of breath with or without hypoxia, sometimes abnormal chest imaging, transaminitis, and low procalcitonin levels. And then of course, stage three, which is the stage that ends you in the ICU, which is a hyper-inflammation phase, which is clinically seen with ARDS, SERS and shock, and cardiac failure. When we look at the clinical stages of COVID-19, we can also look at it from an escalation of oxygen use, with moderate to severe disease having nasal cannula, with escalating disease requiring ventori mask, non-rebreather, and even non-invasive ventilation and invasive ventilation for critical disease. We can also see that these diseases go from the wards or LND to the IMC to the intensive care unit. When we think of pregnant women in COVID-19, we know their outcomes can be worse. Pregnant women have an increased adjusted relative risk of three for admission to the ICU. They also have an increased risk of needing invasive ventilation if they go to the ICU, especially for women age 35 to 44, which is thought to be advanced maternal age and obstetrics. And for women, they have an increased risk of needing extracorporeal membranous oxygenation or ECMO even after ventilation, invasive ventilation. Even more concerning is that in the setting of supplemental oxygen, ICU admission, and even places that can perform ECMO, pregnant women are at increased risk of death. So when thinking about that, we have to ask ourselves, who actually goes to the ICU? And this question is answered by it depends. It depends on so many factors. It can depend on gestational age. So for instance, women that are more pregnant or that have later gestation can be more likely to go to ICU. For example, there are some infrastructures where many patients will go to an IMC or intensive care unit because that's where the negative pressure units are, and that's where the COVID specialists are. There are other infrastructures where pregnant women that require high flow nasal cannula can be cared for on labor and delivery or within an IMC unit, and thus making that infrastructure available for ICUs for only women. So for instance, if a woman is pregnant, she can go to an IMC or intensive care unit. She can go to ICUs for only women that require mechanical ventilation. However, in general, when a patient goes to the ICU, it's so important that a consulting intensivist or critical care team is brought into the clinical care. And when women do go to the ICU, they're most likely going to the ICU because they're not able to maintain oxygen saturation. They require some form of vasopressor to keep their blood pressure up, or they have some organ damage, which can be seen with altered mental status, renal insufficiency, or cardiac disease. So let's talk about the collaborative team for COVID-19 and pregnancy. This involves the maternal fetal medicine specialist or the obstetrics team. It involves the intensivist, whether that's a medicine intensivist, surgical intensivist, or anesthesia intensivist. And it also involves OB anesthesia. It's the collaboration between these groups is even more so important in COVID-19 and critical illness and pregnancy than other forms of critical illness and pregnancy. And I'll give you an example. Before the COVID-19 pandemic, the majority of patients that were pregnant that went to the ICU actually were not pregnant anymore. And what I mean by that is that most of them were postpartum, either immediately or soon after, because the most common reasons for ICU admission in the United States are hemorrhage and preeclampsia. And if you ask any OB if someone's bleeding and they're pregnant, or they have preeclampsia and they're pregnant and they need to go to the ICU, the majority of the time those patients will be delivered before entering the ICU or before their admission. Thus, a lot of the management in the pre-COVID pandemic era was done by the ICU team. However, with respiratory failure and with COVID-19, there is a larger percentage of patients that are actually pregnant at the time of ICU admission. And so this causes a lot more collaboration and a lot more discussion, specifically on medication usage in the pregnant patient, ventilatory strategies in the pregnant patient, and of course, delivery timing and fetal monitoring. So I decided to go forward with this discussion with kind of four simple questions when it comes to special considerations in pregnancy and COVID-19. So the first question being, when is it the appropriate time for a pregnant woman to be intubated? So we've kind of always heard the classic teaching is sooner rather than later. However, in saying that, pregnant women are more likely to be intubated at the time of COVID-19. However, in saying that, pregnancy within itself is not a contraindication to passive proning and or non-invasive ventilation. But as we've already discussed, pregnancy should be considered a difficult airway. So that should always be in the back of your mind that you don't want to have this crash emergency intubation. And so this can create like another conundrum for the intensivist or the maternal fetal medicine caring for these women because you want to hold off intubation if it's safe. However, you don't want it to be this crash intubation in the middle of the night with possibly a less experienced provider. And again, the reasons for the difficult airway include laryngeal edema, the full stomach, and of course, the loss of FRC, making it as I can't say this enough that experienced providers really should be intubating these patients. So when we talk about non-invasive ventilation or even high flow nasal cannula, this is certainly a publication and research gap in the literature. And not only just in COVID-19, but in just in ARDS in general. The most literature that I could find was mainly case series or case reports. And there was one where they actually looked at non-invasive ventilation and sickle cell patients with acute chest syndrome. As you can see, all the patients were within the third trimester or after 26 weeks. As noted here, they all were able to avoid mechanical ventilation. There were no signs of clinical aspiration, and they had relatively shorter ICU stays. But even still, I think whenever any patient is in respiratory failure, especially a pregnant patient where we know that we could have these issues with a difficult airway and massive hypoxemia with induction of anesthesia, we ask ourselves, is non-invasive ventilation or is high flow nasal cannula the right thing to do? And one thing that you can do or you can extrapolate from the literature is the use of the ROCS index. And the ROCS index is a calculation score that looks at the O2 saturation or the SpO2, the FiO2 of the oxygen being delivered, and the respiratory rate. And it makes a calculation. The higher the number, the better. And for example, a score greater than 4.48 is thought to have a low risk of failure. And you take this calculation at multiple intervals. And here, you can say that you take it at 2 hours, 6 hours, 12 hours, then again at 12 hours. And it has actually a pretty good positive predictive value. In a study that particularly looked at the ROCS index, we found that 60% of patients were able to avoid intubation with high flow nasal cannula. However, the patients that needed to be intubated had a 45% mortality. Also, the patients that needed to be intubated had 14% of them required extracorporeal membranous oxygenation, which we'll talk about later. When we look at the numerical values of the ROCS index, higher is better. So greater than 4.88 is a little risk of intubation. From 3.85 to 4.87 is close monitoring due to increased risk of intubation. 2.85 to 3.84 actually states that high flow nasal cannula should be monitored in the ICU. And less than 2.85 states that you should consider intubation. However, I think it's so important to notate that the ROCS index has actually never been validated in pregnancy. And it'll be interesting to look at the ROCS index in pregnancy. The reason is, is because the ratio does not use a specific goal, but it uses the data that's already generated by the patient. And physiologically, the respiratory rate technically does not change in pregnancy. So it really shouldn't alter the ROCS index. However, as we've all seen, with a pertuberant third trimester abdomen, especially with sitting in certain positions, breathing can be quite difficult. And then you add COVID-19, that can really make things very interesting, to say the least. So again, the ROCS index, I think, can be extrapolated for the setting of pregnancy. However, we have to really remember that it's never been validated. And it should be used as more so as a tool in the armamentarium for deciding for restratification of the patient and for role of intubation of that patient. So again, briefly, timing of intubation in pregnancy, the classic teaching is sooner rather than later. Again, to avoid catastrophic intubation or a crash intubation in a pregnant person, non-invasive inhalation and passive proting are not contraindicated and can be achieved in pregnancy. And restratification for intubation, like the ROCS index, can be used, but should be used with caution. Intubations within pregnancy should always be considered high risk, and experienced providers should be the ones that are attempting intubation. The next question, can pregnant women use standard ventilatory strategy for acute respiratory distress syndrome, or ARDS? So when we talk about clinical trials in ARDS and ventilatory strategy, I think there are certainly a lot of clinical trials that have come out. And some of these clinical trials have shown to have a reduction in mortality. However, the clinical trials that I'll focus on today are the ARMA-6, the acute respiratory distress syndrome management with lower tidal volume. There was also the alveoli trial, which looked at the assessment of low tidal volume and elevated in expiratory volume. And then there was the FACT trial, or the fluid and catheter treatment trial. When we look at ARDS and lung protective ventilation, this trial really compared protective or 6 cc's per kilogram of tidal volume for ideal body weight to physiologic, which was 12 cc's per kilogram. When they looked at the comparison of the groups, they found that there was actually a 9% absolute mortality reduction in the lower tidal volume group. However, there were certain trade-offs. Those trade-offs being permissive hypercapnia, or a pH sustained by the body weight, and sustained greater than 7.25, or permissive hypoxemia, or an oxygen saturation of greater than 88%. Now, in saying this, I think it's so important to go back to our initial slides and remember that pregnancy is a hyperdynamic state superimposed in the setting of a respiratory alkalosis. And the reason we have this respiratory alkalosis is not necessarily for the mom, but for the gradient for the fetus. So questions arises, can someone who's pregnant have lung protective ventilation, especially in the setting of allowing for permissive hypercapnia and permissive hypoxemia? So there have been some very, very small studies and mostly opinion pieces that have looked at permissive hypercapnia. And what they found is that they thought that really a PCO2 of 45 to 55 millimeters of mercury seemed to be tolerable without any truly adverse fetal outcomes at time of delivery. They even go on to state that with adequate oxygenation, levels can be tolerated up to 60 millimeters of mercury in the level being the PCO2. When it comes to permissive hypoxemia, this seems to be more controversial. Again, in permissive hypoxemia, the adequate PAO2 is 55 millimeters of mercury or an oxygen saturation of 88%. However, the American College of Obstetrics and Gynecology and the Society of Maternal and Fetal Medicine advocate for PAO2 of greater than 70 or an oxygen saturation of 95%. However, this is not really based on clinical data, but more so translational and basic science data in animal models that look at oxygen saturation. However, the concern is high enough that the sustained maternal hypoxia can cause fetal hypoxia and thus increasing the risk of neurologic deficits in cerebral palsy, something that obviously nobody wants. When we look at decreasing morbidity in ARDS, there's also this idea of liberal versus conservative fluid management. And what I'm showing here is basically a flow chart of the FACT trial. And as you can see, it was clearly very intricate and complex, but I just thought that it would be interesting to show. However, when we look at the liberal versus the conservative fluid management group, we found that really the diuresis and the invasive catheters really didn't cause the patient to be that much more negative. It just kept them from being super positive. So in the conservative group, there was a negative 135 ml difference from admission versus the liberal fluid group, which was seven liters positive. The conservative fluid group had a better calculated lung compliance, less ventilator days, ICU length of stay, and CNS failure. However, there was no significant difference in vasopressor use, serum creatinine, or acute kidney injury. There was also no difference for renal replacement therapy nor mortality between groups. Now, in saying that, putting it all together in pregnancy, furosemide can be given in pregnancy. When we give it in the outpatient setting for women that have long-standing heart failure or dilated cardiomyopathy, we usually will check fluid levels and things of that nature. And the goal is to keep the patient euvolemic. And as you can see, this was really kind of the outcome of this FACT trial. And thus, in pregnancy, one can use diuretics to keep the patient overall euvolemic, but it may not be the case for women who have a long-standing heart failure. And it may not be necessarily within the patient's benefit to completely make them super negative or super dry. However, this is on a case-by-case basis. So that brings up the next question. How do you assess the volume status in pregnancy to make sure that someone's euvolemic? If we go back or we think about our initial slide, we've already said that the patient coming into pregnancy within the third trimester has increased their intravascular volume by 50% to 60%, thus increasing their cardiac output. When we look outside of pregnancy, there are both static and dynamic measures of preload dependence or volume status, static measures being CVP or end-diastolic volume, and dynamic predictors being SVV or stroke volume variation or PVV or pressure volume variation. We can also use IVC variation, passive leg raise, and facile maneuvers. And these can also be used in pregnancy as well. However, they are less validated. When patients are spontaneously breathing, we can certainly use IVC ultrasound and passive leg raise to look at volume status. And when they're mechanically ventilated, pulse pressure variation and stroke volume variation can also be used. However, I think that we all have been in clinical scenarios where we've interchangeably used these measures to look at volume status and not necessarily look for needs of diuresis, but look for needs for if they are hypovolemic or need volume. Outside of using ultrasound to look at cardiovascular structures like the IVC or the projected ejection fraction to look for volume, to look at the clinical use of diuresis, we can also use lung ultrasound, particularly looking for B lines, which are noted here. We can see B lines in the setting of acute cardiogenic edema. We can also see B lines in the setting of ARDS or acute lung injury that can be seen with ARDS from either any form of ARDS like COVID-19 or even bacterial pneumonia. And this can also help with the use of diuresis. However, B lines are thought to be more of a binary, yes, no, whereas volume status can sometimes be a more continuous variable. However, that's also up for discussion and can sometimes needs to have context to that as well. So when it comes to validatory strategies in pregnancy, we can use the target of 6 ccs or 4-8 ccs per kilogram predicted by body weight for ARDS in pregnancy. This can be totally safe and we can look at the pH to make sure that it's above 7.25. However, it is thought that even when we look at the PCO2, that levels of 50-60 may be safe. However, when we look at the oxygen saturation, really most desired oxygenation is to a saturation of 95 percent or somewhere between the 60-80 millimeters of mercury. Another question is, can other salvage modalities be used in pregnancy? So going into the discussion of salvage therapies, I think it's so important to talk about this figure. This figure was taken from the Society of Maternal Fetal Medicine COVID-19 Task Force published in 2021. So as we can see, we've already discussed this, but the pregnant patient can be, of course, mechanically ventilated and they can be proned, they can receive appropriate PEEP, they can receive ARDS protocol for lung protective ventilation, meaning that they can have some form of remissive hypercapnia. O2 saturations are still advocated to be 95 percent. But even more importantly, they can receive sedation. So patients that are deeply sedated can receive different forms of morphine for sedation. Pregnant women can receive propofol, pregnant women can receive fentanyl, pregnant women can receive ketamine, pregnant women can receive dexamethamidine. If it's thought that the patient needs paralysis for synchronization of the ventilator, the pregnant woman in the third trimester can also receive Vecuronium, she can receive Pankuronium, she can receive Citratricurium. So none of those are contraindicated in pregnancy, and I think it's really important to have that conversation because we don't want to withhold medications that can be beneficial to not only the mother, but the baby, making sure that the mom is synchronous with the vent, reducing lung injury to the mom, and reducing hypoxemic episodes is very beneficial to the fetus as well. And so, yes, there can be fetal abstinence syndrome and things like that from being on prolonged use of sedatives, especially with the morphine substrates. However, again, these are usually pretty short, however, this can usually overcome and many NICUs can be accustomed to taking care of these patients and these preterm neonates. However, I do think it's important to discuss that when using sedatives and when using pain medications in the COVID-19 pregnant patient, which we know can use a lot of them, it's important to note that they do sometimes, that they do often cross up placenta and it can make the fetal tracing not look as reassuring. So it's really important to discuss like with your MFM team or MFM provider, what is the normal contextual reassuring fetal heart rate in the setting of deep sedation and even paralysis. Even still, we know that pregnant women that receive all of these therapies appropriately can still have some evidence of refractory hypoxemia and these patients can receive inhaled pulmonary vasodilators they are actually not contraindicated in pregnancy. I think it's important, and we'll talk about this later as well, to consider delivery and consider, I think importantly is controlled delivery at greater than 32 weeks gestation if things are not going well or if there's refractory hypoxemia even in the setting of inhaled pulmonary vasodilators or even consider ECMO if delivery is not considered secondary to very early preterm gestation such as gestation of less than 32 weeks or even at some cases paraviable at 23 to 24 weeks. And we will of course be going over this later in the discussion. But first I wanted to talk about inhaled pulmonary vasodilators in the setting of COVID-19 in pregnancy. So we know that inhaled pulmonary vasodilators can be expensive. There is a small percentage of non-responders the effect is transient. And for the most part, they don't change all cause mortality in patients that have ARDS. However, I think that in the setting of pregnancy, especially the third trimester pregnancy with a viable neonate where delivery is an option, it's important to consider pulmonary vasodilators. The reason is that it can actually give you time for delivery optimization or ECMO optimization. It gives you time to get adequate, if they are responders adequate oxygenation for the mom and the fetus. It can allow for transport to an OR, right? It can allow for transport to another facility that has a higher level of care or an ECMO center or a place where they may even have available obstetrics. And it helps avoid a crash cesarean section which is certainly not what we want. Briefly, when we look at ECMO indications, there are indications by the ESLO guidelines which include hypoxic respiratory failure despite optimal ventilation strategies, which we've discussed. Persistent hypercapnia or a pH of less than 7.2 or a PaCO2 of greater than 80 for greater than six hours. Prolonged ventilation, but less than seven days. Any signs of cardiogenic shock with a cardiac index of less than two liters per minute. A Murray score of greater than three. And a Murray score is seen down here. And it is a calculation that uses the ratio of the arterial oxygen tension or the P to F ratio, PEEP, lung compliance, and chest radiographs. Single organ failure with minimal or no comorbidities. So that means that no other signs of cancer or any other signs of heart disease. No other signs of cancer or liver failure, needing a transplant. Massive pulmonary embolism can be an indication, as well as bridge to cardiac or lung transplantation or cardiac arrest. And in saying that, many pregnant women or birthing persons will meet this criteria because generally most of them are young and healthy, or if they do have comorbidities, their comorbidities are that of chronic hypertension and diabetes. And very rarely before their need for ECMO will they have any end stage diseases that where you were expecting them to not survive within the next year. Although ECMO can certainly be lifesaving, it certainly does have complications. And those complications being anything from bleeding, which can be as high as 25%, leg ischemia that can require amputation, compartment syndrome, infection, surgical site infection, stroke, thrombosis, or even cardiac perforation. And this gives it an overall complication rate of 60%. So again, with the high complication rate, before going to ECMO, it's always important to kind of think to yourself, okay, is this someone that I'm going to deliver before ECMO, or are we going to do like a combined ECMO delivery in the operating room or in the cardiac suite? Briefly, there are two major types of ECMO. So there's venovenous ECMO, which is mostly for respiratory support, influenza and ARDS. And then there's also venoarterial ECMO, which can be for both respiratory support and circulatory support. And the access sites for this are shown below, which can be the femoral artery and vein percutaneously, or axillary, which usually require some form of operation, but it does allow for ambulation. As we've kind of already showed, there can be different types of permutation for ECMO. There is the VA ECMO, which we've already talked about for cardiac failure shown here. There's venovenous ECMO for respiratory failure shown here. And there's also venoarterious venous ECMO, which basically helps with Harlequin syndrome. And really what it does, it's when the ECMO circuit doesn't provide sufficient oxygenated blood to the upper body, this actually causes, this actually brings oxygenated blood through the IVC, which helps support the patient more cephalad. And then there's the venovenous arterial ECMO, which can be secondary to inadequate drainage. And so the ECMO circuit, or one of the venous ports of the ECMO circuit can serve as kind of like a sump to take fluid off to kind of help prevent any cardiac failure or a significant LV distention. When we look at ECMO in pregnancy, we can note that it certainly has been increasing over time. As we can see here, the maternal survival rate is pretty much 0%, and it was only done on three women. However, when we get to 2015 to 2019, the maternal survival rate was 100, and that was the attempts for ECMO was 103 with a maternal survival rate of 75%. When we look at maternal survival rate for acute respiratory distress syndrome, maternal survival rate is 80%, showing that this is certainly a viable option for pregnant women. So the next question is, what is the appropriate fetal monitoring and timing of delivery? So this is certainly a charge question. When we talk about the clinical evidence of ICU admission, use of remdesivir, dexamethasone, and things of that nature, we then have to really start thinking about when can someone be delivered? And when we think about when someone can be delivered, we break it up into the different gestational ages. So of course, there's a pre-viable gestational age, and pre-viable is actually considered to be less than 23 weeks. And when someone is less than 23 weeks, really we would not deliver that patient in that setting. The reason that we would do any type of fetal monitoring would be just to kind of prove or ensure that the pregnancy was still alive. And that intermittent auscultation usually lasts for 10 to 20 seconds and can happen on a daily basis or a weekly basis, depending on where you are or how sick the patient is. However, we would prep the intensive care unit that we would do a paramodum or resuscitative hysterotomy if at greater than 20 weeks. Then there is the setting of viability, which is thought to be greater than 23 weeks. In some places we'll even say 24 weeks to 31 weeks to six, 31 weeks, six days. And during this time, we usually will do at least a daily NST or daily non-stress test unless maternal condition seems to be unstable or there's escalating oxygen requirements. The delivery indication would be for like refractory maternal deterioration status, non-reassuring fetal heart rate, patterns of unresponsiveness, conservative interventions, and of course, hypoxemia or rapid escalation in therapy. The reason that a lot of MFMs will choose a 32 week mark is because there is a significant decrease in severe neonatal morbidity, such as intraventricular hemorrhage, necrotizing endocolitis, bronchopulmonary dysplasia, and all-cause neonatal mortality after the 32nd week. And from 32 weeks to 36 weeks and seven days, if someone has severe illness or is critically ill, especially if they're getting worse, certainly considering delivery after the use of beta-methadone. And beta-methadone is used for fetal lung maturity. And we can, and there are some places that are actually using dexamethasone for fetal lung maturity. And these antenatal corticosteroids actually decrease of all-cause mortality and the neonate decreased the risk of IVH and actually decreased the risk of necrotizing endocolitis. And then of course, after 34 weeks for a pregnant woman who's critically ill, considering delivery at the time of sustained maternal deterioration is certainly reasonable. And with that, that concludes my presentation. I thank you very much. And I look forward to any questions that you guys have in the chat box. Thank you.

COVID-19

pregnant women

critical care considerations

physiology of pregnancy

ICU admission

fetal monitoring

individualized care