Thank you for staying until the end. The last talk is on Mechanical Circulatory Support. I have no relationships to disclose with respect to this talk, which isn't quite the same thing as saying that I have no relationships at all. As with all the talks in this master class, there is a lot of ground we could cover, but I'll try to narrow this down in the next 15 or minutes or so to a clinical focus. As you all know, the circulatory system consists of two pumps in series, the right ventricle pumping into the pulmonary circuit and the left ventricle pumping into the systemic circuit. As such, venous return has to equal cardiac output, not necessarily beat to beat, but on average. Here is a cartoon showing cardiac output and venous return. The venous system is depicted as a bathtub with deoxygenated blue blood. This empties into the right heart, shown as an oval, and is pumped through the lungs, not shown, to become red blood, which is pumped by the left heart through the arterial system and eventually re-enters the veins. In the upper right is Robert Guyton. He taught himself engineering and electronics, but decided he wanted to go into medicine. He wanted to be a surgeon, but he came down with polio, and he became a great physiologist who set up an experimental system that outlined these concepts. I'm not going to describe that system in detail now, but basically, he measured hemodynamics in a large animal model and controlled and varied venous return. You can see some of the raw data in the inset, looking at the relationship between venous pressure and cardiac output. This is shown schematically on the graph. As right atrial pressure decreases, venous return increases, up to a point, at which the pressure is near zero and the veins collapse, something known as the vascular waterfall. This slide introduces the physiologic concept of mean systemic filling pressure, using the analogy of a bathtub. If the drain is at the bottom, then the pressure pushing the water out is determined by the height of the water. Another feature of this model is independence from inflow pressure, not inflow, but inflow pressure. If inflow equals outflow, then inflow pressure does not determine the outflow pressure. I should mention that, strictly speaking, mean systemic filling pressure is the venous pressure you would have if there were no flow in the system, and so this is a concept and not something that can be readily measured in vivo. Another physiologic concept is that of stressed and unstressed volume. Unstressed volume represents volume that fills the venous system before you have enough volume to push against the walls of the veins to generate pressure. In the bathtub analogy, the outflow is not right at the bottom. Fluid under the outflow, unstressed volume, does not contribute to outflow pressure. Now volume is volume, so some people question this deficiency as artificial, but those who argue for the concept use it in this way. Stressed volume may be only 1.3 to 1.5 liters of total blood volume, and some of that is red cells. As such, small changes in venous volume may produce larger changes in venous pressure. The concept of stressed volume may also be used to explain how fluids in venous tone affect venous return. This graphic shows effects of fluids and a venous tone on right atrial pressure. On the top, flow is related to stressed volume. If you give fluids, you increase the stressed volume, and so increase pressure and flow. But as you can see in the bottom, if you constrict the venous compartment, you also increase outflow pressure, and in fact you increase it even more. You can think of venous return as the availability of volume to be pumped. The relevant pressure gradient for venous return is mean systemic filling pressure minus right atrial pressure. And as we saw in the last slide, mean systemic filling pressure is a function of stressed volume and venous compliance. The ability of the left heart to pump volume is expressed by the yellow starling curve. These concepts are explored further in this slide. On the left, mean systemic filling pressure is equal to right atrial pressure. The outflow tube is flat and there is no flow. On the right, mean systemic filling pressure is greater than right atrial pressure, and there is flow downstream from the venous system to the right atrium. The relationship between flow and right atrial pressure is shown on the graph. As right atrial pressure decreases, the gradient between mean systemic filling pressure and right atrial pressure increases, and flow increases. The slope of the relationship, shown by the slope of the bathtub outflow, is a ratio of flow to pressure and is proportional to venous compliance. Now let's take these concepts and apply them clinically. This graph shows what happens when you increase volume. You shift the venous return curve to the right, and cardiac output increases. This graph shows what happens when you increase venous tone. This increases the slope of the venous return curve, and cardiac output increases. Now what happens if you're on the flat portion of the starling curve? Volume will still increase venous pressure and shift the venous return curve, but now there is very little increase in cardiac output. What happens if cardiac function is decreased? Now the starling curve shifts down, and cardiac output decreases. In this situation, cardiac function is the limiting factor. Increasing volume or venous tone doesn't lead to an increase in cardiac output. So how do you know where you are on these curves in a complicated patient? Often you don't, and my bias is that it often makes sense to find out. The other speakers in this session are going to explain some ways in which this might be done. Let's return briefly to the original outline. You have two pumps in series, venous return going into the right ventricle and being pumped through the lungs, and then return from the lungs going to the left ventricle and being pumped through the systemic circulation. Here is the venous way of looking at things. As we saw before, venous flow increases when you decrease right atrial pressure and increase the gradient between mean systemic filling pressure and right atrial pressure. One way to think about this is that the heart functions to empty the venous system and decrease its pressure, and so cardiac output depends on venous return. Actually, in this view, the right heart functions to empty the right atrium and lower its pressure, raising the gradient between mean systemic filling pressure and right atrial pressure. There is a countervailing view among some physiologists, and I want to do it justice. The venous system doesn't actually generate any pressure by itself. The walls have tone, but they don't pump. The pump that generates pressure in the systemic circulation, which includes both the arteries and the veins, is the left ventricle. And so this is an LV-centric view in which the left ventricle is what drives blood through the venous system into the right atrium. I think there is room for both views to help explain physiology in different situations. So let's put this all together if we can, in a clinical context. In shock, we need to think about volume management, contractility, and potential support of the right ventricle. Hemorrhagic shock is all about volume management, and Dr. Kaufman is going to tell you more about volume assessment and fluid management in various settings. I'm going to talk about the complexities that arise in patients with cardiogenic shock. We're going to talk about volume management, contractility, and right ventricular support. You are probably well aware that in cardiogenic shock, fluid administration isn't a good thing for the left side. We saw that if you were on the flat portion of the Starling curve, pressure goes up a lot, but cardiac output doesn't. As it turns out, fluid isn't all that good for the right side either in many situations. The literature advocating volume administration as a first step in patients with right ventricular failure draws from the work of Dr. Luis del Italia. This paper does show some initial increase in cardiac output with fluid administration in right ventricular infarction. But what is often forgotten about these papers is that there is a limit to this. Once the wedge pressure gets up to 18, additional fluid did not improve cardiac output. Now let's talk about contractility. In cardiogenic shock, you don't always know whether you have a problem in left ventricular function, right ventricular function, or both. In fact, biventricular failure was most common in the landmark shock trial. So it can be hard to pick a therapy, and importantly, a dose, out of the air. If you do that, and what you are doing is working, I guess that's okay. But if it isn't, doubling down and making another guess may not be the best thing to do. You probably need more information, which you can get in a number of ways. Echocardiography, hemodynamic assessment, or maybe better, both. This is a hemodynamic measure of right ventricular function, the pulmonary artery pulsatility index, which is calculated as right-sided pulse pressure, P.A. systolic minus P.A. diastolic pressure, divided by right-sided filling pressure. These data come from patients with MI in cardiogenic shock, and you can see that PAPI distinguishes patients with right ventricular failure from those without, with reasonable specificity and sensitivity. So, three take-home points from this talk. Venous return is important, since without it, there is no cardiac output. Both volume and compliance contribute to venous return. Consideration of right ventricular function may be important as well. It may be more important to consider how this talk might change your practice. More appreciation of the determinants of venous return may encourage more thoughtful assessments of volume status in critically ill patients. Venoconstrictive or venodilatory effects of vasoactive agents may be as important as arterial effects in some contexts. A more integrated approach to cardiac function, considering both the RV and LV, may improve therapy.

venous return

cardiac output

circulatory system

mean systemic filling pressure

stressed and unstressed volume