All right. Well, thank you, everyone, for joining and having me. Hopefully, we'll wrap this session up, and you can enjoy the rest of Congress. So I'll be talking about the medical treatments that we should consider or, I guess, potentially consider in patients with RV failure on VV ECMO. That's really—I have no disclosures that are relevant to this, and we'll discuss the possible medical treatments for RV failure during VV ECMO. And so, really, just to recap, there's a number of pathologies that might continue to persist once someone goes on pump for VV ECMO. Some of these things include there could be a persistent hypoxic pulmonary-vasoconstriction, despite having maximal support on ECMO and the ventilator, continuous non-pulsatile ECMO flow across the tricuspid valve. Perhaps there's atelectasis in the setting of reduced PEEP and ultra-low ventilator settings. It could be an ongoing pulmonary-vascular dysregulation. Many of these patients have untreated or really partially treated pulmonary emboli or microvascular thromboses, and some of these can actually persist during ECMO and be a result of ECMO. And then, also, they may have partial correction of metabolic derangements, could have persistent hypercapnic acidosis, or many of these patients are septic and have metabolic disorders. And so, really, there's—unfortunately, outside of these pathologies and treating these direct reasons for why your patient might have RV dysfunction, there, unfortunately, isn't a go-to drug that can really solve right heart failure. But what I'd hopefully like to talk about today is some potential strategies that we might be able to deploy and some rational decision-making that might help, in a way, at least protect the RV and temporize things. And so, the first thing I would like to talk about is nitric oxide. Nitric oxide is a pulmonary-vascular smooth muscle dilator. It's quickly bound up by hemoglobin and plasma proteins, and so it has a very short-lived effect, and also has a localized effect when given by inhalation in the pulmonary-vascular tree. This is a very interesting study of pigs, where the pigs were—administered a hypoxic gaseous mixture to induce arterial hypoxemia, so a PaO2 of less than 60, as well as an increase in their pulmonary artery pressure of 50% above baseline. And after this, they administered nitric oxide to the pigs, and they assessed some of the pulmonary mechanics. And what you can see on the left-hand side is that after incrementing doses of inhaled nitric oxide—20, 40, and 80 parts per million—the Pa pressure is reduced, and the RV power output reduced. And, of course, as you'd probably expect, when you withdraw the nitric oxide, then these things return to baseline. They also assessed the transpulmonary-vascular efficiency. That's what you see here on the right. This is calculated by the total pulmonary artery blood flow divided by the RV power that is required to generate that flow. And so you can see, after they administered inhaled nitric, there was improvements in the transpulmonary-vascular efficiency, really in a dose-dependent manner, up to 80 parts per million. And this similarly reduced back to baseline once the nitric was withdrawn. This is an interesting case out of the Netherlands. They had a gentleman in his mid-40s who was put on ECMO with ephemeral IJ cannulation for COVID ARDS. And initially, the patient had good biventricular function and just had persistent hypoxemia once they went on pump. And a few days in, they were struggling because the recirculation fraction was around 50%. And this was despite the cannulas being in a quite optimal position. And so they did an echo, and the RV was severely dilated. There was severe tricuspid regurgitation. They initially tried inhaled prostanoids without really much effect, and so they trialed nitric oxide. I believe they gave 30 parts per million. And you can see that, after nitric, the recirculation fraction reduced over the course of 24 hours. And the arterial hypoxemia also marginally improved. All of the ventilator settings and all of the ECMO circuit settings were essentially maxed out at this point, and they held it constant during this period of nitric oxide use. And then they did an echo 12 hours later and saw that the RV was of normal size and there was no residual tricuspid regurgitation. Another area that we can potentially have an impact is with buffering. So many of these patients have persistent hypercapnic acidosis if we can't crank the sweep high enough. And bicarbonate is challenging in this situation because bicarbonate buffers by dissociation to dissolved carbon dioxide that then traverses cellular membranes and produces an intracellular acidosis and may contribute to impairment of myocardial contractility. Tris-hydroxymethylaminomethane or THAM is a non-bicarbonate buffering agent that actually buffers by protonation and it generates this ammonium complex that is then renally excreted. But most importantly, THAM does not generate carbon dioxide when it buffers. This is a nice study that was done here at San Francisco General where they had a small cohort of patients with ARDS, mainly septic shock and some liver failure, but they had persistent hypercapnic acidosis and they gave some of them THAM and some bicarbonate. You can see that the THAM improved the arterial pH. It improved the arterial CO2 and it improved the base deficit. And sodium bicarbonate essentially did the exact opposite of this. It worsened the acidosis. It increased the CO2 and it worsened the base deficit. Another potential strategy is through careful selection of vasoconstrictors. If we have concomitant systemic hypotension, this is a study where they took isolated human pulmonary artery and radial artery ring segments and they exposed these arteries to increasing dosages of various vasoconstrictors. They're all listed here on the right. And what they measured was the proportion of total contractions at each dose or concentration of vasopressor. And what you can see on the left-hand side is that all of these vasopressors really, as you would expect, all contracted the systemic artery. And when you look at the right, they all contracted pulmonary artery, but vasopressin did not. And so vasopressin could serve as a strategy to rescue systemic pressures without the consequence of an increased reventricular afterload. And these effects were replicated by a group in a clinical setting. So this is a small cohort of patients following cardiac surgery that had refractory vasoplegia. They were already on nitric oxide for their high PA pressures. And they had persistently low MAPs despite norepinephrine administration. And so they gave them vasopressin and then they measured some of the systemic and central hemodynamics. And so what you can see in the first two panels here is that one hour following vasopressin administration, obviously as you would expect, their mean arterial pressure increased by just about 20 points. And there was essentially no effect on the mean pulmonary pressure. And then if you look at the, these are also corroborated with the two panels on the right where, of course, the systemic vascular resistance significantly increases and there's no consequential increase in the pulmonary vascular resistance. And then I think most interestingly, if you look at the center panel, this is the proportion of pulmonary to systemic artery pressure. And this was significantly reduced after the administration of vasopressin. And then I'd like to close out by discussing inotropes again. You know, we talked about this as potential strategies to mitigate RV failure or at least temporize it and maybe avoid going on ECMO. But if you're on and maybe careful selection here can make a difference. And so this is a study where they randomized patients to receive either dobutamine or milrinone. And they gave them variable doses with the ultimate goal to achieve a similar increase in cardiac output. And then once that was achieved, they measured all of these variables. And what they found was that both of these agents, both dobutamine and milrinone, increased the right ventricular ejection fraction and had a favorable effect on the RV and systolic volume with milrinone to a greater extent. But then they also looked at the peak PA pressure, which you can see that milrinone reduced the peak PA pressure, but dobutamine did not. And this was significantly less than both milrinone at baseline and the comparison to dobutamine. And also the similar effect was seen with the PA and systolic pressure. And so milrinone might be an interesting strategy in an attempt to reduce right ventricular afterload and prevent these consequential PA pressures and have better RV systolic performance. And so in summary, the medical therapies for RV failure during ECMO should be individualized. Obviously the first thing that you should do is identify what the reason is for your RV failure and attend to that cause. And there's unfortunately no drug that can really do this and treat RV failure, but we have demonstrated that nitric oxide reduces PA pressures and improves RV efficiency. And also it might be reasonable to avoid the consequential increases in pulmonary vascular resistance and hypercapnia through the careful selection of various vasoactive agents and buffering agents. So with that, I think we'll take questions at this point. Thank you.

RV failure

VV ECMO

pulmonary-vasoconstriction

pulmonary emboli

milrinone