Good morning, everyone. We are so thankful that you guys are hanging around for the last day. How are you guys enjoying the conference so far? Thank you very much. Again, my name is Bhavin Dalal. I'm one of the pulmonary critical care sleep physician at Beaumont Health in Michigan. And I have three esteemed speakers for this particular topic of PH, PH, and right ventricular failure. I think I'm the least experienced. I have Sandeep Sahai, Steve Mathai, and Jean Helving. We are going to twist the order of the presentations a little bit to match the objectives. So Jean is going to go first and will talk about the hemodynamic assessment, especially with the PA catheter data. Then Steve will talk about pulmonary hypertension in acute settings. I will talk about pharmacological or medical management of pulmonary hypertension in RV failure. And Sandeep will talk about the pre-op and specific scenario assessment. So with that, I will start with Jean. Thank you very much again for coming. All right. One thing I would like you to do is get out your calculators, because you're going to need it. All right? Closer. Is it better? Yeah. All right. I always talk a little bit quiet. It's because I had five sisters. And if you weren't quiet, no one heard you. So I'm going to talk about how to evaluate these folks. And I want you to get a little tachycardic during this presentation, because I want you to feel this nervousness you'll get when you see these patients. All right. I have a few disclosures. I'm going to talk a little bit quietly. What I want you to do is recognize the echo features that should prompt you to say, I got to have a right heart cath. And then know how to proceed with that right heart cath and see the pitfalls you might face when you're interpreting the data. And you could go totally the wrong path. Okay, we're going to talk about my friend who's 42 years old. He has mixed connective tissue disease and he comes into the ER short of breath as heck. He's having chest tightness, lightheadedness with stares and he's passed out twice. He has very, very high risk symptoms if he indeed does have PAH. He's dyspneic with any routine activities and sometimes at rest. So what is he functional class for? He's on a few medications, amlodipine, omeprazole and hydroxychloroquine. Those are all for his mixed connective tissue disease. And he's hypotensive tachycardic and his saturations are not where they should be for a healthy person. So when you examine him, some JVD, he's a heave, he's tachycardic, he has a loud P2 and a 3 of 6 murmur. That is the exam on a test for pulmonary arterial hypertension. But you're worried about this gentleman. You listen to his lungs. They're clear. So you don't think this is probably pulmonary edema. His abdomen has fluid in it, shifting dullness and it's moderately distended and he has 2 plus edema. All right. So ER has requested a bed. They get some other labs. BNP is high, sodium is low, creatinine is high. All of those are markers of poor outcomes in right heart failure. Chest X-ray has a big heart. You don't want to do a CTPA because he has a high creatinine, but you do a VQ. He's stable enough from that perspective in the ER and there's no acute PE. CT, you're not sure why they got that, but there's no significant infiltrates. And he got a bedside echo and the ER doc was scared. And so he called the cardiology and said, hey, can you come down here and do a real echo for me? And then next step, he calls you, the ICU doctor, and says, please come and help me with this patient. I'm not sure what the right thing to do is. You said, OK. I'll come down. Get that echo image up for me. And so that's your echo. You have a pericardial effusion, a big RA and a big RV. You look at the rest of the report, the left side looks OK. And then you say, I want to see that one other favorite image of mine, the peristernal short. And it makes you even more worried. And why? You can fit that whole LV in the RV and have room and you have a nice pericardial effusion and a D-shaped septum because that's a volume and pressure overloaded right ventricle. You look at the TRJ and you and your head are going to calculate. You're going to take that TRJ velocity, times it by itself, times it by 4 and add it to a high right atrial pressure because you know that right atrium is big. And you got at least 85. All right. So are you going to get a right heart cath? They've been telling you for the last 10 years you don't need them, right. You can do this all on your own. You don't need hemodynamics. But there's a little bit of information that's helpful from the Nationwide Readmission Database that tells us in 200,000 patients, 10% of them getting right heart catheterizations. Those patients were more complex, but they did better when you had hemodynamics. So they had lower risk of death and stroke. And their 30-day readmission rates were lower and they had better survival. So let's think again about right heart cath in the right hands. This is not something that you do when you don't have experience and you don't know how to use it. It is a very dangerous tool. It's like driving without a license. You shouldn't do it. Okay. You're going to get your hemodynamics. And if you haven't done one of these in a long time, you've got to really look at them. You have your right atrial pressure that tells you about the health of your right ventricle. And then you go up and you get this sine wave that looks like a right ventricle. And then you notice your diastolic pressure goes up, and that's your PA waveform. And you get a dichrotic notch. You've got to see all of these things or you aren't sure where you're at. Because a lot of times you don't have a fluoro bed in the ICU. And then you drop down. You drop down. Remember, you drop down and get your wedge. Doesn't stay at the same level as your pulmonary pressure. Okay. So you get two tracings and you're like, what the heck? I do not know what to do now. I've got a pulmonary pressure of 51 over 24 with a mean of 23 and a wedge of 29. And then I do it again and it's 60 over 30 with a mean of 40 and a wedge of 14. One of these is physiologically impossible. Which one is it? Which is physiologically impossible? So your PA diastolic and your wedge can't be in the way the first tracings are. You can't have a higher wedge than your PA diastolic because look at this nice tracing. You have your PA waveform. You wedge it and it decreases, right? So this is the first pitfall. That first thing you'll get, you'll get that high wedge and you'll call cardiology and say it's left heart failure. Even though you know, you know what it is. You saw that echo. You know that's precapillary. But this happens all the time, right guys? It's terrible. And I've literally had a young man sent for a heart-lung transplant from a local hospital because of this. And it turned out he had PAH and got on PH therapy. So just remember that it is erroneous if your wedge is higher than your PAD. So first step. Okay. So now you say, I want to know exactly where I should measure this. Do I measure it at A, B, or C, okay? I want to measure this when there's no forces in the chest. So if you're going to relax, where are you going to be? At full inhalation, full exhalation, or are you going to be at just relaxed exhalation? Of course, right? As I said in our PG course, think of yoga, okay? When you're spontaneously breathing at end exhalation, you want to measure. And why? Because you're going to get the wrong answer if you don't measure in the right place. And where do you want to measure? You want to measure at the A wave. So this is not for the weak. Measuring these tracings determines the outcome and you've got to know all these parts. Okay. And then you open your book and you look at your right atrial waveform and you're like, oh, my A wave should be at the P wave. Uh-uh, not in the wedge. When we're occluding that pulmonary artery and we're seeing transmitted pressures, our A wave is a little bit after the QRS. Sometimes you can't figure out where it is. So you've got to know where it is in that EKG cycle, okay? So now I know. I'm going to go to my EKG, I'm going to drop down a little bit beyond the QRS and I'm going to see the A wave here. And I'm going to measure the top of it, the bottom of it, and get the average of it. So we have now four steps to get the right wedge. This is your biopsy for PAH patients. All right. So now we're going to get our full cath and now we're really worried. Why are we worried? We've got high pressures, of course. But we've got a low cardiac output and a low mixed venous saturation. These are high risk. So now I want you to calculate the pulmonary vascular resistance. You can do it in your head. Remember, it's your mean pressure minus your wedge divided by your cardiac output. It's 15. So if you got the wrong wedge, you measured not at the A wave, you measured at the wrong place in the respiratory cycle or the wrong place in the cardiac cycle, that's going to be wrong. All right. So this is important. You've got to act fast. All right. Our management could have been deleterious. You could have decompensated this patient if you treated them improperly. Person went to the ICU, got on some nitric, bridged them to EPO, and you started low-dose pressers of inotropes, supported, you diuresed. You actually called ECMO because you should call your ECMO colleagues to bridge this patient to recovery. This is a young person. And they can be on standby. You also thought about a transplant, but the patient got better really fast. So you didn't have to proceed there. OK. So that is the first person to get you tachycardic. Now the second. And we are doing OK on time. We've got a 22-year-old who came to the ER for syncope. She's short of breath. She passed out twice, once when she fell and once when she was carrying a 35-pound bag of dog food. She was admitted to the trauma team. Her vitals are relatively stable on admission, but she has some signs of right heart failure on exam. All right. What happens? What do you think happens on the trauma team? She gets exactly what she needs to go the wrong direction. She gets more hypotensive. They give her more fluids. They're concerned about tamponade. Thank goodness they didn't tap the effusion. And she's in the 70% range, and they say, please come help me. OK. What do you recommend? You say, hey, fellow, run and get that echo machine. I got to see what this right ventricle looks like. Now this one actually scared me to death. This is one of my patients who is doing very well now. I mean, do you know what that first image is? That's the left ventricle. I can fit more of them in the right ventricle. All right. It probably wasn't that bad when she came to the ER, but got much worse. OK. So what are you going to do with her? You're going to cath her. You might cath her in the ICU, because you're scared to death to move her. The problem is you get a wedge of 50, and you know that can't be real, because it's higher than your PAD, and you know better. You looked at that echo. 95% of the time, as clinicians, we are right. There's actually data on that. And then we get ourselves all mixed up by erroneous data. So these are actually worse, too, right? Lower cardiac index, lower right atrial saturation and pulmonary artery saturation. So she is, by her echo and her numbers, in a very bad situation. OK. So what are we going to do? We can't even calculate a PBR. We're going to talk to cardiology. We can either go back in and get a wedge set, right, and see if we're right. We tried that. It was 60%, so we weren't wedging. Or we can look at an LVDP. So we don't lose when we ask for an LVDP. It's not uncommon that our wedge is hard to obtain, either in our chronic PE patients or our new, really severe patients. All right. So where do you measure the LVDP? I'll show you right here. And it correlates with the A wave of the wedge tracings. And that was proven in the 70s. This is actually a tracing from that paper, showing us that they correlate well. And we saw that yesterday in our network presentation on right heart catheterization. So how often is it wrong? Well, this is a Halperin study from 2009, looking at more than 10,000 caths, and about half the time, we need help with an LVDP. Now if you do all of these things I mentioned, you will get more accurate. But still remember, if this doesn't make sense to you clinically, ask for help with an LVDP. Or if you're a cardiologist, you can do the LVDP. So now we calculate. It matters. Now our pulmonary vascular resistance in this person, 15. All right. This person's in big trouble, too. We are going to take a similar approach. This person's going to have ECMO on standby, and I did have that, and this individual. And this person actually did go for a transplant evaluation, and by the time she was followed up once, she was too well for needing a transplant. But you've got to have all these things, because you're not going to win every time. How often are you not going to win? Well, this is Steve's data from Hopkins. We can get people out of the hospital, but in 12 months, all PAH, expert, expert, expert study is setting, do poorly. So we've got to be ready for them to not respond well long term. We're lucky if we win, as I said, but we don't always. In this study by Hopkins, they found that there was significant mortality, and the ICU mortality was about a third. Okay. So this is very challenging to manage. We're going to talk about different aspects. We've got to address all aspects, and we've got to get the right information to get the optimal result. So we've got to be ready for us to be great clinicians, right? We've got to be on it. But we also have to have our friends as backup with our mechanical support and our transplant options. So with that, I thank you, and looking forward to the next speakers. Thank you. me to present. Let's see if I can open this up. Okay. So I've been tasked with discussing pulmonary hypertension in the ICU in about seven different clinical scenarios. And given the time frame, I'm going to focus on two of them just so we can have a discussion and learn a little bit, hopefully, about this. Here are my disclosures. I'm going to present the case. A 72-year-old woman with scleroderma-associated PAH on Tadalafil and Ambrosentan. Paroxysmal atrial fibrillation on anticoagulation. Was admitted with subacute onset of dyspnea, cough, and purulent sputum. She has also a history of diabetes, had a cholecystectomy. Her vital signs are shown here. She's febrile, borderline pressures. The heart rate is 110 and irregular. Was 88% on room air and felt to be in moderate distress. Her lab data are here, showing a high white count, a lowish hemoglobin, a low sodium, a high creatinine, an elevated pro-BMP, and lactate. And looking back through her records, the most recent right heart catheterization on combination therapy with Ambrosentan and Tadalafil from about six months ago show a PVR of about 4.3. So mild to moderate pulmonary hypertension at that point. She ultimately was intubated in the ER for hypoxic respiratory failure. Broad spectrum antibiotics were started, cultures obtained, IV fluids were started, and additional data were collected. So the first piece of additional data was this. So what about arrhythmias, particularly atrial arrhythmias in patients with pulmonary arterial hypertension? What is the impact on them? Well, first of all, SVTs and pulmonary arterial hypertension are quite common. These are some older data looking at the cumulative five-year incidence of atrial arrhythmias in patients with PAH. And as you can see, at five years, about 25% of PAH patients who were followed prospectively had developed some form of atrial arrhythmia. This was replicated in another cohort, again published in around 2014, showing that 40% of the arrhythmias in this population were related to atrial fibrillation, about a third had atrial flutter, and other atrial arrhythmias were in about another 30%. So it's fairly common to see atrial arrhythmias. What about causes of admissions to our ICU in PAH patients? And this is the paper that Gene referenced earlier. In our population, 12% of the admissions to the ICU in PAH patients were related to arrhythmia. And in-hospital mortality for those patients was about 20%. So it's not insignificant in terms of its potential impact on outcomes. Well, why is that? What is so deleterious about atrial arrhythmias in patients with pulmonary arterial hypertension? There are a couple of studies that have tried to look at this. And mind you, this is a difficult thing to describe. But in this study from Paul Forfia's group, tried to parse out the relative contribution of atrial contraction to RV function. And in this study, using echo-based measures, they found that in a normal right ventricle, about 20% of RV function is dependent upon normal atrial contraction, similar to what we see in the LV. But when you have a diseased RV, like you would have in someone who has pulmonary arterial hypertension, it's about 50% of RV function is dependent upon normal atrial contraction. So this is why, when you get called to the ER for a patient of yours who has pulmonary hypertension, is in the emergency room, has a new onset atrial arrhythmia. This is why those patients need to be admitted, because their RV is going to decompensate when they go into an atrial arrhythmia. So how do we treat atrial fibrillation or flutter in PAH? Well, the guidelines would suggest we should restore sinus rhythm if possible. And I think that, in general, the community, both in right heart failure and in left heart failure, are considering the importance of restoring sinus rhythm over rate control. But I would advocate, particularly in our patients with PAH, that we achieve rhythm control. Now the specific recommendations are really lacking evidence, but in general, our practice is to avoid beta blockers and calcium channel blockers. The knee-jerk response to a patient who has new onset atrial arrhythmia is to give patients these medications. These medications are negative inotropes, particularly for the right ventricle. And you can have someone spiral into right heart failure if you are not judicious with the use of these medications. We prefer medications such as amiodarone. I know that's a shock many times when we tell the ER, no, we prefer amiodarone. They're like, you're a lung doctor. How can you give somebody amiodarone? They're going to get fibrosis. The rate of lung toxicity in patients who receive amiodarone is pretty low. It's on the order of 1% to 2% risk, and particularly if your dose is less than 400 milligrams a day, which is what our patients are going to be on most of the time. So I personally do not have an issue with amiodarone. I'm curious if the panel has alternate thoughts about that, but I definitely do recommend amiodarone for our patients. And if amiodarone for any reason is contraindicated, digoxin for rate control may provide some benefit to RV function. So there is some older literature, actually a randomized controlled trial demonstrating improvement in RV function in patients who have PAH. Obviously this is not a first-line therapy, but it might be adjunctive therapy for a patient who has chronic RV dysfunction and atrial arrhythmia. So atrial fibrillation is resolved, but you're called back to see the patient because the blood pressure slowly drops and the patient becomes more hypoxic, and the echo looks like this. So now this patient has developed right ventricular failure, right heart failure. This is older data from our previous study looking at our experience with ICU patients and PAH. Overall, the mortality was 14%, and in the ICU it was 48%. So we've made some strides. At that point, if you had PAH and got admitted to our ICU and required mechanical ventilation, it was a very, very poor outcome. And it's not just short-term. Gene showed data from our more recent study looking at the long-term outcomes. This is parsed out by connective tissue disease PAH versus patients with idiopathic disease, and it's cumulative mortality on the y-axis. And as you can see, our connective tissue disease patients are particularly at higher risk of having poor outcomes. So what are the things that were predictive of outcomes in our PAH populations? So interestingly, things that we would expect. Systolic blood pressure less than 100. Your odds of death were not as high as one might expect, but in your serum sodium, as Gene pointed out with the example that she presented, if you had a serum sodium less than 136 on admission, you had a fourfold increased risk of death. So hyponatremia is a known predictor of outcomes in PAH in general, but may be even more important in patients who are in the ICU. If you had renal dysfunction, your risk was also increased. Now, how does that compare to our friends on the left side of the heart? I think this is a pretty interesting comparison. So if we look at patients who are admitted to the hospital for left heart failure, and this is older data from a conglomeration of several studies on the left here, we see that the combination of a systolic blood pressure and a renal dysfunction, if you had both a systolic blood pressure less than 100 and a serum creatinine of greater than two, your risk of death in hospital mortality was 16%. We compare that to our data from right heart failure, and if you had a systolic blood pressure less than 100 and evidence of renal dysfunction, your in-hospital risk of death was 41% of the population died. So it's a significant issue in our patient population. How do we manage this in a patient who has ARDS, as I would argue this patient's presentation and imaging and physiology suggests? Well, hemodynamic failure is very common in ARDS. 60 to 70% of patients will have hemodynamic failure, and it's commonly related to RV failure. The pulmonary vascular dysfunction is related not only to the underlying disease that is pre-existing, but also to hypoxia, release of inflammatory mediators, microvascular thrombosis, direct endothelial damage, vascular remodeling, and loss of functional lung volumes. These are all things that occur in ARDS and manifests clinically as a rise in PAP and PBR. Importantly, 25% of ARDS patients will have severe RV failure with mortality rates of 60 to 70%. These are our most vulnerable populations. So how do we approach these patients? Well, the three principles are optimize preload, reduce afterload, and optimize contractility of the right ventricle. This is a nice consensus statement from several years ago now that I would refer you to regarding the management of hemodynamics in patients with ARDS. One of the figures there I find quite instructive. So looking at pulse pressure variation as a guide to understand whether someone is fluid responsive and perhaps is exhibiting more sepsis physiology versus a patient whose hemodynamic failure is related to their pulmonary hypertension and increased RV afterload. So if you assess someone's PPV and found that they don't have a significant increase, then perhaps those are patients you would think of having increased RV afterload as the driver of their hemodynamic instability. And steps should be taken to address that, which I'll talk about next. So what are the things we can do to reduce this afterload? Well, the one thing you can do is look at your patient and look at the vent. So number one, thinking about the role of hypoxia. There is a significant hypoxic vasoconstriction that occurs. This varies not only by the PaO2 level, but also by the pH. So these curves here demonstrate the differences in PVR, percent increased PVRs on the y-axis relative to your PaO2 by pH. So as you can see, if you have a reduction in your PaO2 below about 50, you're going to have a significant increase in your PVRs. You need to address that. So we often target our saturations a little bit higher potentially than we would in our other patients to minimize this effect. What about mechanical ventilation? Well, at either extreme, whether at over distension or at low lung volumes, the pulmonary capillary bed is at risk. Either over distension leading to compression or at low lung volumes you're going to have collapse. And both of those things can influence pulmonary vascular resistance. So you want to think about your tidal volumes perhaps even a little more carefully in this patient population than you think about in other. Well, maybe not more, but you want to think clearly about this because there might be situations where you want to ensure that the tidal volumes might be a little on the more generous side than you would traditionally treat somebody who has ARDS. You want to make sure your plateau pressures are low to minimize over distension or under distension collapse. And then you want to avoid permissive hypercapnia. So this is one of the strategies and one of the issues with pulmonary arterial hypertensions or patients with RV dysfunction. Hypercapnia stimulates increased pulmonary vascular resistance as well. So you want to minimize that in these patients. Keep the PEEP around less than or equal to 10 if possible. And then if these interventions are not working, sometimes prone positioning can improve VQ matching and also has been shown to improve right ventricular function in patients with critically ill. So what about RV perfusion? We're going to have a little more discussion about vasopressors. I'm going to just spend one moment talking about the potential role in this particular scenario with someone with pulmonary arterial hypertension and ARDS, why this might be helpful. This paper was referred to me by one of our faculty when I was a fellow. And I cringe because it's about dogs and volume expansion. But I find myself referring this article to my fellows now. And I'm sure they had the same kind of cringe when I sent it to them. But in any case, this is a very interesting study that looked at the role of volume expansion versus norepinephrine in dogs that were experimentally given pulmonary hypertension. And in this study, if you gave volume, stroke volume decreased, blood pressure dropped. If alternatively, you gave norepinephrine, stroke volume increased and pressures improved. So we used these data to kind of support our hypotheses or practice that norepinephrine in particular might improve not only RV contractility, but also improve outcomes in our patients. One other finer point that I think has become more and more difficult to achieve is thinking about RV perfusion in the setting of anemia. I tend to view these patients as more of a cardiology heart failure paradigm, where we try to keep hemoglobin closer to 10, rather closer than 8. And I know that we're supposed to be judicious with our transfusions. But I do believe that thinking about these patients through that lens and getting their hemoglobin closer to 10 might also improve their outcomes. This is from, again, a nice review thinking about pulmonary arterial hypertension and ARDS from a couple of years ago that summarizes what I just reviewed here. There are potentially modifiable factors, gas exchange impairment, hypoxia, and hypercapnia that we can improve upon with our ventilator management. Interstitial and alveolar lung edema, thinking about fluid and hemodynamic management. Lung heterogeneity with collapse or overdistension, again, focusing on our tidal volumes, our PEEP, and whether or not there's a role for prone positioning. And then pulmonary vascular mechanics, thinking about the role of reducing afterload through medications, which we'll talk about shortly. And then thinking about other things regarding lung heterogeneity and prone positioning that might help with this. So back to this patient. She initially was treated with amiodarone with restoration of sinus rhythm. Her right ventricular failure was treated with judicious fluid management. She did receive norepinephrine, and we optimized her ventilator. And she was extubated five days later. She was DC'd home 10 days after that. So with that, patients with PAH and, honestly, PH are prone to develop atrial arrhythmias that are significant short-term and long-term consequences. Aggressive pursuit of return to sinus rhythm should be undertaken, and patients with PAH and PH who develop ARDS are particularly prone to right heart failure and poor outcomes. So measures aimed at minimizing exacerbating factors and enhancing strategies to improve pulmonary vascular function should be pursued. OK. And with that, I thank you for your attention, and hopefully we'll have time for questions at the end. Thank you very much, Steve. Before I proceed, I have a disclaimer that some of the slides, you will see some repetition because evidences are the same. I can generate a new just in the next one minute. So with that, my name is Bhavin Dalal, and we'll talk about the pharmacological agents or medical management for acute right ventricular failure in ICU. As you guys can see that all of they have some disclosure because they are rich people and I'm still poor. I have no, nobody's giving me money. I don't have any money. So in this session, we will try to make you understand the pathophysiological aspects of the right ventricular failure and explain the role of the pharmacological agents. I also have some of the audience response questions. So if you guys can pull out your phone and start working on, that will be helpful. So I have this patient who is a 50-year-old female, came with a shortness of breath, baseline functional class 2 or 3 symptoms, has a scleroderma-associated PAH, and she's on azathiopharynmal scleroderma and embryosyntellar fill for the last four months and still kind of optimizing treatment. Now presented with high-grade fever, cough with expectoration, and right-sided pleuritic chest pain. Of course, the x-ray does show the right middle lobe pneumonia. I would like you to pay attention to this hemodynamics for this patient in the serial orders. So right now, her heart rate is 110, blood pressure is low, oxygen saturation is low, respiratory rate is high, and temperature is high. So I have a question for you guys. I mean, sorry, the two liter of IV fluids were given. The patient was started on antibiotics. The patient was also started on IV norepinephrine, not able to restore the blood pressure, so added vasopressin. So the first important principle of treating RV failure in ICU is treat the underlying cause. I think Steve, again, mentioned that. What are the common causes we do see in pre-existing PAH patient? For example, sepsis, motor vehicle accident. If a female patient or young female patient become pregnant, is a huge issue and a topic of discussion by itself. In a worse scenario, patients can have a worsening of PAH itself, either a disease progression or they are not compliant with their medication, which also is a difficult issue to resolve. So treat the cause is the first underlying principle if we can. So this is now we are progressing forward. This is day one. As Steve mentioned, 25% or 30% of the people do develop atrial arrhythmias. And we know from our critical care literature that with sepsis, around 25% of the people without even PAH do develop atrial arrhythmias. So the atrial arrhythmias or AFib is very common. So patient did develop atrial fibrillation. The blood pressure is slightly better. The oxygen saturation is better after the antibiotics and all those things. So after the development of AFib, what will be the next best intervention now? Steve actually highlighted a few principles, so I'm pretty sure you guys are adaptive learners or quick learners. So start metaprolol, start diltiazine, stop norepinephrine, stop vasopressin. So I think if I let's see, yes, it looks like it's working. This is a second time for the last seven tests this is working. So I'm so happy. If you guys can take your phone and try to answer the question. Excellent. I think that you guys are so smart people. I don't need to teach you much. Stop norepinephrine will be the best choice if the blood pressure is reasonably OK. We don't need to unnecessarily have a potential factor. So this leads to the second principle of a treatment known as improve the surrounding environment. And Steve did cover a few of the things. So what we can improve? Number one, try to manage the arrhythmias. And I'm not going to go in detail at all because Steve did an awesome job about it. The second is a ventilator management. So as again he mentioned, avoid high pressures. Sometime if the oxygen saturation is pretty good on a low FiO2, you can even lower the PEEP less than some. I mean, as I said, volume is an issue, not a PEEP. So try to avoid the pressure by cutting down on the PEEP as much as possible and maintain the adequate oxygenation and maintain a good metabolic profile. Again, Steve did discuss about this pH issue and vasoconstriction. And we are again showing the same curve that at a lower level of PO2, your pulmonary vascular resistance is exponentially increased with decreasing pH. So say, for example, a patient has a non-NNNGAP metabolic acidosis, you probably want to improve the pH by itself by giving some bicarb or something because the pH will have independent action on the vasoconstriction. So again, moving forward, this patient on a day two or three, patient after the stopping norepinephrine, atrial fibrillation is converted to sinus rhythm. See, we have a lot of differences in a patient. His patient did receive amiodarone. My patient did not. But ultimately, the sinus rhythm is restored. Vasopressors are stopped. Blood pressure is controlled. Lactic acid is normalized. Unfortunately, one of the common denominator between that patient and this patient is this one, deteriorated now further in oxygenation. And now patient is requiring 50% high flow to maintain a 90% to 94% saturation. So you can see that the heart rate is good, blood pressure is good, but the oxygen saturation deteriorated and the respiratory rate increased. The X-ray is showing this instead of pure right middle lobe pneumonia. So what will be the next intervention? IV furosemide, IV renal dose dopamine, IV vasopressin. Let's see if the poll works. I think it does work. It's fantastic. OK, and I think nine out of 10 times in the patient with a pre-existing PH, diuresis works. So we give more fluid, all of us, and the hospitalist and the ER, everyone. So the fluid, and we are drowning people. So try to be very careful with the fluid administration. So that leads to the third principle of the management that optimize the RV function. So one important reason by which we can optimize the RV function is the fluid management. And again and again, we are saying that the fluid management is very critical, because when there is a significant fluid overload in the pre-existing PH patient, the septum is going to move towards the left. RVDP, LVDP, both will increase, and cardiac output is going to go down. If we diuresis the same patient, septum will start moving forward towards the right side again. Cardiac output will improve. And the creatinine will improve. Everything will improve. So this is an indirect physiology of cardio-renal syndrome. So every time I teach my residents and fellows that when we are giving diuresis, and as long as the creatinine is improving with a negative balance, I think you are moving in a positive direction. That's a key factor we just need to understand again and again. The second part of the RV muscle perfusion, or RV perfusion, how can we make that better? The two important principle, when the RV is overloaded, either volume overloaded or pressure overloaded, there is a significant decrease in blood supply. So look at this particular picture, and you can see that when the systolic blood pressure, the aortic pressure, is reduced, LV is very resilient. LV is awesome. The LV flow, or LV coronary flow, is not much affected. But the RV flow goes in garbage. RV is very sensitive to reducing the aortic pressure. So whenever the decreased supply happens, we have to probably improve the aortic pressure, and we'll talk about that. Second is because there is a massive RV overload, there is a massive increase in demand. And if you think the RV overload as a stroke volume times the PS systolic pressure, for example, 60 times 20 is 1,200 units of a RV workload, inpatient with a pulmonary hypertension, the stroke volume has gone down, and PA pressure has gone up. And if I put some hypothetical numbers, 30 ml is a stroke volume which is reduced from 60, and the PA pressure has been increased from 20 to 80, your RV workload is 2,400 units, which is double. So remember that every time this particular mathematical equation will help us, that the RV function can be improved by the aortic pressure as well as reducing the workload. So my patient on a day five, now patient has a sinus rhythm, blood pressure is, heart rate is good, WBC normalized, lactate is, patient has a negative fluid balance, high flow nasal cannula was weaned, now she's on a, 94% on the four liter, but now the blood pressure has started to drop to 80 to 90 systolic and 50 to 60 diastolic, and the lactate increased. In the previous lecture we just learned that the inner patient with PAH, when the lactate is even marginally increased, pay attention to it, that's very important part. 2-D echo did show the worsening RV dysfunction, so what will be the next best intervention for this patient? This is probably the last question. IV epinephrine, IV dopamine, IV dobitamine, or IV milrinone? Excellent, this is what I expected. I guess I should give us one more choice, all of above. But by the new ABM criteria, we are not doing that. So I think I will say IV milrinone for the time being, but none of the other options are absolutely wrong. As Steve mentioned, we have a paucity of data by the evidence. Why am I saying milrinone? To improve the RV contractility is based on this particular study. The number one important concept, we all realize that the blood pressure is low. We need to improve the blood pressure by every means. There is no question. Which agent do you choose, that's controversial. But improving blood pressure is no doubt. Steve actually showed the same paper from 1981 or 84 from the docs. And this way, just I'm highlighting the numbers in a normal, when the coronary driving pressure is normal, in a venous section of the heart in a dog, the lactate level was 17.6. Now look, if the coronary driving pressure has gone down from 65 to 23, lactate has increased by almost fourfold from the venous circulation. And as soon as we added the phenylephrine and improved the coronary pressure, then again, the lactate came back to the normal. So very important, a basic science study shows us that the coronary driving pressure is very important. These are the agents you can use. For example, milrinone, dobitamine, epinephrine, they all come with their own flavors of positivity and negativity. Why? Again, I'm saying I did choose milrinone because in one of the study, in a head-to-head comparison, again, this is only a very small one study, so you shouldn't take home this message in a very positive manner. But the milrinone versus dopamine, the cardiac index was much better with milrinone compared to dobitamine. And similarly, the mean PA pressure was much better with the reduction of a mean PA pressure was much better with the milrinone compared to dobitamine. Overall, compared to the baseline also, the mean PA pressure and PVR in the subset of a population where the pre-existing PA was present, they have a significant improvement with the milrinone. So based on this particular study, I'm saying that the milrinone might be preferable over dobitamine. But again, dobitamine is not a wrong choice. So one simple principle is follow the heart rate and follow the lactate. If one agent is not working, you might have to change the next agent. So if milrinone is not working, try to change it to dobitamine. If dobitamine is started and it's not working, try to change it to the milrinone. And so you can mix and match, and then you can go ultimately follow the heart rate and follow the lactate. If those things are improving, things are improving. With that, I will say Sandeep will talk more about little pomeri vasodilators. Thank you very much, guys. Thank you, Bowen. And thanks for inviting me. Good morning. I'll be, I think, by now, what? So my topic is a little bit different. So I'm going to talk about the perioperative and preoperative assessment of PH patients when they have to undergo any surgeries and how to optimize their PH and how do we get them safely go through a procedure. And whatever I'm going to discuss, I was actually attending the previous session with acute PE. I realized there is a lot of evidence in acute PE, a lot of trials and systematic review as opposed to in this area, there is a lot of expert-based opinions and anecdotal opinions. And you can see Steve had to show a dog experiment study from 84. You could see that the evidence is sort of kind of lacking and it's more about the experience and observational studies and that. And recently there is a, I think I've seen this after a long time, one consensus statement about perioperative care of PH patients. So again, we'll discuss a little bit about that. So these are my disclosures. Okay. I'm so envying all of these guys. I'm just making sure he sees all of them. Okay. So in this session, we'll cover management of PH therapies during perioperative period in the hospital. And I'll have a couple of cases to kind of walk you through that. And let's start with the cases. The first case is of 74-year-old woman with connective tissue disease, PH, who fell and broke her hip. This is very common in elderly patient populations. Scleroderma isn't this prevalent in the population. And PH medications were Tadalafil, Mesitentin, and inhaled Treprostanil 12 breaths, four times daily. On home oxygen, function class three, diagnostic PVR was 11-wood unit, which improved to around six-wood unit after six months of treatment. Comorbid issues, AFib at baseline, retains a little bit of CO2. For that, she's on home BiPAP, hypertension. Preoperative echo, now she comes to your ER and gets admitted to the hospital with broken hip and has to undergo an emergent surgery. And this is the last echo which you have from your last clinic appointment, RV function near normal, normal size, no pericardial effusion, TAPC around two. Also plans a surgical intervention under general anesthesia. The last BNP at your last evaluation was 40 and walk distance was 376. So with this patient, now you are in ER and she needs to undergo a surgery. How would you approach this patient? So the question here is about, obviously, the PH medications. And the patient is on inhaled Treprostanil. So my question to you, how do you want to continue this? You stop it and let her continue with the orals only for the time being until she gets the surgery done. You transition it to IV prostacycline. You continue inhaled Treprostanil because you feel missing few doses won't affect much. That's fine. And you transition to other treatment options like inhaled Ipoprostanol or inhaled nitric oxide. How do you? How do you? I think just to give this one before. OK. Great. That's all. Okay, well actually, I'm pretty pleased with those answers. I felt like anything can be done, but the safest option could be, transition to IV prostacycline could be the safest option in these patients. But again, this is what highlights the lack of evidence in this area, and that's where the kind of expert center role and the expertise of the physicians who are managing these patients comes into play. Again, like transition to IV prostacycline, probably the safest option. Now, the question comes, and Bhavin wanted me to highlight this, that how, talk a little bit about how to initiate the parenteral prostacycline in PH patients, and not only perioperative period, but even if you have to start, again, it's a weight-based calculation, dedicated central venous access for delivery of the drug to right atrium or SVC is needed. Intravenous supraprostanol versus triprostanil, there is no stronger data, but patient factors, your individual experience can play a role to pick the agent. You slowly initiate one to two nanogram per kilogram per minute dosing, and titrate as tolerated, and close hemodynamic monitoring with heart rate, blood pressure is needed during that time. In our hospital, we do it on our floor, PH floor, but again, it's institutional policy. You have to, if you are not comfortable, you can move these patients to ICU. You can start these drugs in the ICU setting, or at whatever is the safest environment, and then monitor for the patient tolerance that they can tolerate. They develop a lot of side effects, like nausea, headache, flushing, so you monitor, and you continue to titrate the dosing as per their tolerance. So this is another case who presented to ER, a woman with PAH, 67-year-old, with diverticular perforation, and needs an emergent abdominal surgery. On her last PH clinic visit two months ago, she was on oral PD-5 inhibitor, ERA, and parenteral prostacyclin at dose close to 60 nanogram. She was in function class three, BNP 250, walk distance was 310 meters, and echo showed severely dilated RV with significant dysfunction, and pericardial effusion, small pericardial effusion. Now, how do you classify this patient? Is it high risk or low risk? That's, there are only just two options. It should be 100%. Yeah. If it's not, we have to start chest all over again. 100% of the board of faculty. OK, great. Yay, we can go home today. So clearly, this patient is high risk. And unfortunately, she fell. I mean, she had a bowel perforation and had to undergo a major abdominal surgery. So one of the basic things is current guidelines recommend that you should continue the PH medication. That's the basic principle. Now, how do you want to do? Like in the first case, we talked about patient was inhaled on inhaled triprostanil, you would like to transition it to. Or actually, if your institute has inhaled lipoprostanil or nitric oxide, those could have been the other options. But continuing PH medication is important. If your patient is going to be NPO around the perioperative period, you could use IV options. PDE5 inhibitors are available in IV formulation, so they can be used. Only ERA which can be crushed through and given through the OG or NG tube is basentin. But practices may vary center to center on that. But current label indications is for the basentin that it can be crushed. High risk patient, like the second case which I discussed, those should be transitioned to IV prostacycline, definitely. Low risk patients can be transitioned to other inhaled agents, like inhaled lipoprostanil, like I mentioned earlier. Anticoagulation in this patient is required due to hip surgery to minimize her risk for thromboembolism, like the first case which I discussed. But like standard of care, anticoagulation for DVT, prophylaxis, and all is warranted in PH patients like any other surgical patients. So how do we proceed with the preoperative evaluation and management of these patients? Consider the risk in PH, like how bad their pulmonary hypertension is. And remember that the risk increases with the inability of the dysfunctional RV to accommodate for rapid changes in the ventricular preload and afterload and contractility. And I think Steve, Bobbin, and Gene, all of them, in pretty detail, they explain the role of afterload and preload. They discuss about the fluid and how the reduction in afterload for RV will help in optimizing the RV function. So always keep that in mind. And you have to make sure that your RV function is optimized to the level that your LV gets enough preload to maintain the systemic blood pressure and meet the systemic oxygen requirement. My simple thing when I go into ICU to fellows resident is common things are common. Keep things simple. That maintain normal blood pressure, maintain good oxygenation. You don't need to reinvent the wheel or try to look for zebras here. All the disease is zebra. But keep things simple that you maintain the normal blood pressure and oxygenation. Volume shifts, that's very important. And I think we highlighted that earlier in the other talks. Anesthetic agents, that's always controversial. But trying to avoid the agents which could suddenly decrease the vascular tone significantly, or systemic vascular tone, SVR reduction, those kind of agents should be avoided. I think mechanical ventilation, Steve already discussed, Bobbin also discussed about the PEEP and platelet pressure. The strategies about the mechanical ventilation. Changes in the sympathetic tone can precipitate worsening in RV and worsening of PAH. Again, that's why it's be careful about using the anesthetic agent, what kind of agents you are going to use during the surgery. We generally make a recommendation to our anesthesiologist, although it's hard to get hold of them. But we still do. And tell them not to use agents like Propofol or something where you can suddenly, even in the induction phase, you could suddenly reduce the SVR significantly, especially in our second case, which was a high-risk patient. And obviously, maintaining the perfusion. We talked about the ventricular ischemia, RV ischemia, or RV dysfunction. Now, this was about the patient and the disease. But at the same time, the surgery also matters. That what surgery your patient is undergoing. And that also puts the patients at a variety of risks. So you need to know about your patient, what type of PAH your patient had before going to the surgery, what was the severity of pulmonary hypertension, RV function, comorbidities, arrhythmias, we discussed, which is a very important factor to decompensate patients with PAH. And so, as I mention all these things, it's very important that PAH patients, when they are undergoing a surgical evaluation, we consider them for the multidisciplinary team, a preoperative risk assessment, determine the PAH phenotypes, whether they are true group one PAH, or mixed phenotype, or multidisciplinary planning, discuss case with your surgeons, or whoever is doing the procedure. Then preoperative hemodynamic optimization, if you have time, but in emergent cases, you probably won't have time to do that. Then intraoperative management, and we will discuss these factors about the induction agent, maybe using inhaled agents for induction purpose. And then postoperative management and ICU care, which was very nicely covered by my colleagues. So this is the risk assessment, the patient factors, you determine how their PAH is well controlled, if you are planning an elective surgery for your patient, look for their function class two, their function, what their, or the low risk status, look for signs for right heart failure, then do the basic testing, BNP, chemistry, make sure their kidney function, everything is optimized, ECG to show there is no arrhythmias, six minute walk test, which is, as you may know, for PAH patient evaluation is a very important tool, surrogate for their functional capacity assessment, perform that and make sure that they are in stable and it's consistent, or improving from their prior walks, if they are being treated actively, and so optimize their PAH. This consensus statement recommends doing an echo within two weeks of the planned surgery, and right heart cath in a selected patient. I generally do a right heart cath wherever I feel the function is not normal, or I know patient like very stable, I do a right heart cath before sending these patients for any elective surgeries and see what their hemodynamics is, so that you have room to optimize their treatment, or PAH, before you send them for surgery. So, this is general guidance about how you define a low risk patient and high risk patient, clinical symptoms of right heart failure, functional class one or two, who could walk more than 400 meters, and if you have facility for CPET, or if you are too much into exercise physiology, you could do CPET. You could look at the echo, MRI imaging, hemodynamics, as I mentioned, and these are the parameters you would look for to make sure that they are low risk or high risk, and then biomarker, BNP level, and pH risk score, and I'm not sure if you are familiar, there are a variety of risk stratification scoring for PAH, the United States-based REVEAL scoring, if you have not heard of that, and there are European scoring, ESC, ERS, so you could use those tools and utilize them in risk stratification of these patients. Now, this is the surgery specific risk, low risk procedure, any procedures with local anesthesia for minor procedures, dermatological surgeries, like mainly elderly patients needing cataract surgery, for example, I consider that as a low risk procedure, and I could easily clear them for that. Endoscopic procedures, those are short duration procedures, routine colonoscopies and all, they are considered as a low risk procedure. Look at the high risk procedure, emergent major surgery, so our second case was definitely a high risk surgery, which that woman needed, and her RV function was not, she was high risk patient undergoing, or needing a high risk surgery, so that makes it very, very high risk patient situation at that time, cardiovascular surgeries, if your patient needs liver transplantation, and I'm not going into detail, that's a whole total spectrum of patients, if you need a transplant, any other organ transplant, and you have PAH, but any other surgery where you anticipate large fluid shifts, and that's very important that you discuss that with your surgical team, and your anesthesia team, and also your ICU team, before you subject these patients to undergo these surgeries. Now these are some general consideration for perioperative, and I think one of the important thing is if you have time, and you are in a community setting, you discuss with your nearest expert PH center, and possibly transfer these patients over there to get their surgery done. Those centers who are familiar with managing PH patients during these situation. Sometimes in emergent situations, it's very challenging, whether you want to transfer the patient, or you want to get it done at your local center, and again, this is very much individualized decision at that time, what situation you are in, but I think it's reasonable to have a conversation with your expert PH center that this is the situation, and that probably will be very helpful in your decision making, and also for your patient. Abrupt interruption of PH specific therapy can lead to rebound pulmonary hypertension, so please avoid doing that, and that is not recommended by the guidelines. As I mentioned, transition to inhale pulmonary vasodilators during perioperative period is an attractive option, and many institutes nowadays have them available at their facility, so you could use that. Inhale nitric oxide works very rapidly, it's through the activation of cyclic GMP, and relaxes pulmonary vasculature, resulting in decrease in PVR, and drop in mean pulmonary artery pressure, but again, it has to be weaned. If surgery is done, and later on, you have to slowly wean it, do not abruptly stop it. Consider transitioning to oral therapy once patient is allowed to take oral medication. Some oral prostacycline analogs can be easily transitioned to IV formulation, so that will be helpful for you. Again, the take home in the end, I would say risk stratify your patient, manage these patients at expert care center. General anesthesia is best avoided. PH specific therapy should be continued, and again, it's an individualized care for your patient, the surgery they need, and the resources you have at your disposal, so make that multidisciplinary decision for your patients. With that, thank you very much for your time and attention. Thank you.

pulmonary hypertension

management

perioperative assessment

RV function

multidisciplinary approach

ICU management

atrial arrhythmias

mechanical ventilation

blood pressure

individualized care

PH