My name, again, is Lakshmi Sridharan, and this afternoon I'll be discussing the hemodynamic management with respect to intravenous vasoactive medication. I have no relevant financial disclosures. So our roadmap for this discussion, IV vasoactive agents and cardiogenic shock, and looking at a few unique, but quite common, hemodynamic situations, such as right heart failure, perioperative settings such as heart transplants, and bradyarrhythmias. And then we'll look at a very different hemodynamic profile in acute heart failure with a hypertensive phenotype. Today, I will not be discussing primary inotropic agents in detail, because you will get an excellent lecture on inotropy. So let's first begin by thinking about various hemodynamic profiles of shock in general. So when we look at four large categories of shock, you see the distributive shock, of which sepsis is a part, has a relatively classic signature when it comes to a low SBR. But cardiogenic shock really has a classic signature for all four parameters of hemodynamics. It's typically thought to have a high SBR, a low cardiac output, high LD filling pressures, and a low contractility. Understanding this profile is important because it informs how we think about the goals of managing cardiogenic shock. As with all forms of shock, the number one goal is systemic circulatory support, meaning keeping the map up to maintain cerebral perfusion pressure, and secondarily, of course, renal perfusion pressure. In cardiogenic shock, based on the hemodynamic profile, we begin to think about this concept of ventricular vascular coupling, where we're essentially looking at arterial elastins and a framework to consider contractility in the context of ventricular load and thinking about efficient ventricular function. Each ventricle has a different amount of myocardial fibers and support and has a very different vascular bed that affects its afterload. The right ventricle is coupled to the pulmonary vascular bed, and the left ventricle is coupled to the systemic vascular bed. Then, of course, another large tenant of management in cardiogenic shock is coronary perfusion in the cases of ACS, for example, acute coronary syndrome. The first goal, as with all forms of shock in cardiogenic shock, is maintaining the systemic circulatory system. We talk about vasopressors here. We have our classic vasopressors, norepinephrine, which is a strong alpha, epinephrine, which is a strong everything, dopamine, classically used in cardiogenic shock, particularly in years past, phenylephrine, strong alpha-1 agonist, less commonly used in the cardiac intensive care unit, and vasopressin. Below that, I have listed three inotropes that I won't discuss in detail today and allow you to learn in your subsequent lecture. When we discuss vasopressors, dopamine at low doses is considered to really work on dopamine receptors and perhaps have some renal vasodilation. At higher doses, perhaps more alpha receptors. This has classically been used in cardiogenic shock in the distant past because there was thought to be some type of renal protective effect that we now know is likely not true. One of the benefits of dopamine at some of the lower medium doses is that it provides a fair amount of inotropic support. We can look at levophed, and though levophed is considered a slam-dunk first-line pressor in septic shock, the same can't be said of cardiogenic shock. There was a trial, the SOAP2 trial, that was published in the New England Journal over a decade ago where a specified subgroup analysis was done of cardiogenic shock where there seemed to be less 28-day mortality when levophed was used as the first-line pressor over dopamine. However, this trial had several limitations including the lack of an operationalized definition of cardiogenic shock and a lot of unreported treatment variables with respect to coronary reperfusion and also the grouping of several types of hemodynamic profiles. As you'll see in cardiogenic shock, hemodynamic dissimilarities are very important in assessing which vasoactive agents you pick first. Vasopressin, an excellent vasopressor that has less pulmonary vasoconstriction and no inotropy, so could be preferred in situations where systemic arterial support is required while trying to decrease RV afterload. Epinephrine is rarely used in the cardiac intensive care unit except in a couple of situations such as in hypertrophic cardiomyopathy, particularly in the setting of obstruction, critical AS in the time period where a patient may be awaiting an intervention, and very rarely in recalcitrant ventricular tachycardia where any level of inotropy is worsening the ventricular tachyarrhythmia. Epinephrine, of course, is the pressor of all pressors, incredibly strong inotropy and pressor support. It can be used and is often used in the CICU setting for RV support because the RV can be particularly challenging to provide inotropic support to. So in cardiogenic shock, then the question arises, which pressor is the right pressor? Unlike septic shock, there is no slam dunk first line and second line pressor. You have to think about how the left ventricle is doing versus the right ventricle. What are the filling pressures in each ventricle? What is the stroke work? And how is the associated arterial vascular bed doing? Is the PVR very high? Do you need to think about supporting the systemic vascular resistance while decreasing the pulmonary vascular resistance? And this concept of using a pressor as an ischope, for example, with dopamine or epinephrine, will reemerge over and over again. And so the answer is that in cardiogenic shock, the right pressor is really based on the individual hemodynamic profile. And in cardiogenic shock, there is always a low threshold for mechanical circulatory support because there are limitations to what vasoactive agents can really provide. In end-stage cardiac patients or in post-cardiotomy patients, folks can present with vasoplegia, where actually the SVR is quite low in the context of a relatively low cardiac output and index. And this completely changes the profile of what first-line vasoactive agents you may use. When you look further into types of cardiogenic shock, right heart failure emerges over and over. You had a great lecture discussing the hemodynamic assessment of the right heart. In acute RV failure, and again, I'm specifically referring to acute RV failure, such as an acute PE or acute right ventricular infarction, the ventricle is very preload dependent. And so you may actually always look to target a higher CVP, more like 10 to 12, sometimes higher, depending on what you're looking at. And inotropy will become important but is very challenging for the RV. And as I mentioned, sometimes epinephrine is used for this reason, though often not the setting of an acute RV infarction from an acute coronary syndrome. The RV is very afterload sensitive. And you do need to think about pulmonary vascular bed vasodilation, either via inotropic choices such as milrinone, that is a PD inhibitor, and therefore may have some pulmonary vasodilation, or more targeted inhaled or intravenous pulmonary vasodilator therapies, such as NO or prostacycline analogs or endothelium receptor antagonists. Mechanical circulatory support in the setting of RV infarction, such as an impella RP or catheter-directed therapies, as in the case of acute PE, may be your best choice when trying to support acute RV failure. When you think about chronotropy, when all you need is a little more heart rate, the clinical scenarios of this can be really in the perioperative cardiac surgery environment. For example, in heart transplant surgeries and in the intra-op postoperative time, bradyarrhythmias, brugada for example, isoproteranol is a fantastic pure chronotropic agent. Sometimes its limitations in a CICU setting are that often we're not looking to increase heart rate in a cardiac ICU, except if a patient truly is having a torsad or bradyarrhythmia scenario, and isopril usage can be limited by instances of hypotension. Sometimes we use dobutamine in these scenarios as well for chronotropic support. On the other side, we have heart failure with a hypertensive phenotype. The most common is when you see heart failure with preserved ejection fraction, or HFPAF, but you can see this with acute mitral regurgitation or acute aortic regurgitation as well. Typically, these patients present in acute pulmonary edema in the setting of elevated afterload where systolic blood pressure should be over 90. I would say, before you start considering IV vasodilator therapies, the MAP should also be greater than 70. In most of these scenarios, particularly in HFPAF, you are now managing diastology. These are challenging cases with recurrent admissions where, once again, you're looking at the mitral inflow patterns on echocardiography to determine the extent of diastolic dysfunction and left heart filling pressures. IV vasodilator therapy is probably not the best option for routine use in heart failure with reduced ejection fraction. Clinical indications for IV vasodilator therapy in acute heart failure by the guidelines, as I said, in patients with blood pressures at least over 90 systolic and without symptoms or other evidence of hypotension or malperfusion. It can be used to reduce congestion and as an adjuvant therapy for diuretics to relieve dyspnea. Also, in the scenario of hypertensive emergency or symptomatic coronary disease or hypertension following coronary revascularization. So if you do have a patient presenting with this phenotype of heart failure with hypertension, what are the intravenous vasodilators you can use? So assuming a systolic blood pressure greater than 90, and I would advise clinically a MAP greater than 70, you have several agents at your disposal. Nitroprusside always comes to mind first. It's a sodium salt of a fair cyanide and nitric acid, and its reduction leads to local production of NO. The use of NiPri really requires an arterial line because the onset of action is rapid and it can be very potent. It is a balanced vasodilator and it can reduce the pulmonary vascular resistance, but you must be cognizant of the cyanate toxicity risks. Nitroglycerin is very popular in the cardiac ICU setting. It is a venodilator at lower doses, meaning that it will reduce preload. But at higher doses, it can reduce systemic vascular resistance as well. Pharmacologic tolerance can develop with longer use of nitroglycerin. It's cleared by the vascular endothelium. And in the CICU setting, it's often preferred because it causes direct coronary vasodilation. So it can be used in cardiogenic pulmonary edema from an MI, for example. Nacardipine is a calcium channel blocker that is a vasodilator. It will not reduce filling pressures very well because it doesn't have much of a venodilator effect. Intravenous hydralazine is best preserved for pregnant patients who are presenting in hypertensive urgency, in part because hydralazine is safe in pregnancy and also because it is not the best agent for acute heart failure and other scenarios. There is an intravenous ACE inhibitor formulation available in the United States, but it's not commonly used, in part because it's not studied very robustly in acute heart failure, and the risk of hypotension is quite high. The most important learning points of vasoactive agents in cardiac critical care is that hemodynamic assessment is key. Essential hemodynamic profiles determine your pressor choices and your inotrope choices, and if and when you can get away with using a pressor as an inotrope. Remember the concept of ventricular vascular coupling. Each ventricle needs something different, and each ventricle is coupled to a different vascular bed. You need to be targeting each ventricle and each vascular bed in the fashion that it requires and based on its own resistance and filling pressures in order to optimize the efficiency of the ventricle and its associated vasculature. In cardiogenic shock, vasoactive agents can have limited role, especially when cardiogenic shock is advanced, and mechanical support should be thought of early and often because of these limitations. IV vasodilators have a very specific role in volume overload and hypertension and are likely not a great first-line choice in routine HFREF. Thanks so much for your attention, and happy to take any questions.

hemodynamic management

cardiogenic shock

vasoactive medication

ventricular vascular coupling

mechanical circulatory support