Medical management of heart failure was briefly discussed in LV failure part 4. The medical management of any shock should be addressed in terms of oxygen delivery. Cardiogenic shock occurs when there is not enough oxygen delivery for the patient’s demand due to decreased cardiac output related to the heart. The primary problem with oxygen delivery is hemodynamics but also the decrease in organ perfusion. Hemodynamically there is a drop in stroke volume leading to the hemodynamic derangements shown in Figure 1.
Figure 1: Breaking Down Cardiogenic Shock Hemodynamic Problems
The problem with perfusion is that the decrease in blood pressure drops the pressure gradient and reduces blood flow to the organs. This means that the medical management must optimize hemodynamics and maintain perfusion. Additionally, the oxygen delivery must be higher than the oxygen consumption. If the delivery is unable to be increased appropriately, another way to meet oxygen delivery goals is to decrease consumption.
Figure 2: Oxygen Delivery vs. Oxygen Consumption
Cardiogenic shock problems to be addressed:
A. Decreased oxygen delivery:
1. Increased preload
2. Decreased contractility
3. Increased afterload
4. Hypotension/Poor perfusion
B. Increased oxygen consumption
A. Decreased Oxygen Delivery
1. Increased Preload
When there is decreased stroke volume this leaves more volume in the ventricle which increases preload. When there is too much preload, the myocytes get overdistended which decreases the ability to contract and worsens stroke volume. Additionally, the decreased perfusion decreases lusitropy and the ventricle loses its ability to relax and worsens preload.
Medical management: The ideal medication would be a venodilator that has positive lusitropy. Dilating the venous system will decrease the amount of volume returning to the ventricle and will lower the preload. Most venodilators have lusitropic properties which will allow more ventricular relaxation.
2. Decreased Contractility:
When there is decreased contractility, the ventricle has problems ejecting blood forward. This leads to decreased stroke volume and worsens cardiac output. As stated in LV contractility, contractility is independent of preload and afterload, but the function, or ejection fraction, can change with alterations in preload and afterload. Medications can be given that increase the contractility or squeeze of the myocytes.
Medical management: The ideal medications are inotropes. Inotropes are divided into whether they increase or decrease the afterload. Inodilators are medications that increase contractility and arteriodilate. Inopressors are medications that increase contractility and vasoconstrict.
3. Increased Afterload:
When there is decreased stroke volume and cardiac output, the body recognizes the decreased flow and blood pressure and responds by increasing the constriction on the arteries to help keep the blood pressure up. This response is helpful in other forms of shock, but vasoconstriction will worsen the stroke volume and cardiac output in cardiogenic shock. Reversing this will allow the heart to empty easier and improve function and cardiac output.
The most important hemodynamic component to focus on in congestive heart failure, decompensated heart failure, or cardiogenic shock is reducing afterload. If afterload reduction can be achieved and tolerated, these patients will do significantly better.
Medical management: The ideal medications are arteriodilators. These medications preferentially dilate the arterial system instead of the venous system. Some medications are dose-dependent and will venodilate at lower doses and arteriodilate at higher doses.
4. Hypotension/Poor Perfusion:
To be able to reverse the shock, the patient must be able to perfuse their organs. Perfusion is defined as the blood flow to the organs and relies on the pressure gradient across the organ. A drop in the pressure gradient reduces blood flow and decreases organ perfusion. Organ perfusion is usually said to be mean arterial pressure (MAP) minus central venous pressure (CVP), with a goal MAP ≥ 65mmHg.
Systemic perfusion = MAP – CVP
Coronary perfusion is different and is MAP – left ventricular end-diastolic pressure (LVEDP).
Coronary perfusion pressure = MAP – LVEDP.
The goal is to keep the MAP at normal levels to ensure perfusion. Sometimes adding an inotrope can increase the blood pressure without adding vasopressors. However, often, vasopressors are needed to ensure an appropriate MAP.
As mentioned in part 2, patients can have a large cytokine release leading to vasodilation and third-spacing. Therefore, these patients are often misdiagnosed as having septic shock and may require vasopressors and be fluid-responsive. This typically lasts 12-24 hours but can last for several days.
Medical management: The ideal medications are vasopressors. Not all vasopressors are equal. Vasopressors will squeeze the arterial system and will add resistance that the ventricle must overcome. This is only beneficial if there is vasodilation or, if the MAP is < 65mmHg, it is given despite being detrimental in non-vasoplegic hypotensive cardiogenic shock.
B. Increased Oxygen Consumption
Most medications that are used to increase blood pressure or increase contractility of the heart will not decrease oxygen consumption. There are medications and alternative forms of treatment that can reduce consumption.
1. Sedatives:
This is a wide range of medications, but they will decrease the metabolic demand of the patient and therefore decrease oxygen consumption. Most of these medications will also have a side-effect that may limit their use in cardiogenic shock.
Dexmedetomidine - Bradycardia
Propofol - Decreased inotropy
Ketamine - Catecholamine release/Increased afterload
Midazolam - Increased mortality
2. Paralytics:
This can be added to patients after sedatives and pain medications are added. This will further decrease oxygen consumption by paralyzing skeletal muscle. This obviously has long-term consequences with severe weakness.
3. Non-invasive/Invasive Ventilation:
Supporting a patient’s breathing and the positive pressure it provides has multiple effects. 15-20% of a patient’s cardiac output can go to the diaphragm during high work of breathing. By supporting the patients breathing, it will reduce the work of breathing, decrease oxygen consumption, and allow the cardiac output to go to other organs.
Additionally, positive pressure will reduce afterload and improve forward flow.
Medical Management Options:
Venodilators: Nitroglycerin
1. Nitroglycerin can be beneficial in heart failure in multiple ways. Nitroglycerin is first a venodilator, it is dose-dependent. The typical dose started does dilate the coronaries and increase lusitropy of the ventricle but does not cause arteriodilation. The dose must be greater than 100mcg/min to get appropriate arteriodilation. The starting dose for nitroglycerin is usually 10-20 mcg/min compared to sublingual nitroglycerin which is 0.4mg or 400mcg per dose. Low dose (<100mcg/min) nitroglycerin will venodilate and increase lusitropy which will decrease preload.
Arteriodilators: Nitroprusside, Nitroglycerin, Nicardipine
1. Nitroprusside is an almost pure arteriodilator. This makes it the ideal medication for afterload reduction in patients that can tolerate the decrease in blood pressure. It also is a positive lusitrope. Nitroprusside has been shown to be superior to inotropes in the treatment of cardiogenic shock. This is because it allows the heart to empty without increasing the work of the heart, which occurs when adding inotropes.
2. Nitroglycerin must be at high dose (≥100mcg/min) in order to arteriodilate. This can be very effective at both preload and afterload reduction, but often causes hypotension that limits its use.
3. Nicardipine is not a typical arteriodilator used in cardiogenic shock. I included it in this list because it is more of an arteriodilator which is beneficial, but nitroprusside is superior. One benefit that nicardipine has is that, in many hospitals, nitroprusside cannot be concentrated and nicardipine can be concentrated. The amount of volume infused with higher dose nitroprusside can make it not as effective, but cardiogenic shock doses are typically low and still make it the first choice in this category.
Inodilators: Milrinone and Dobutamine
1. Milrinone has many benefits, it increases contractility, increases lusitropy, and improves relaxation, it decreases pulmonary vascular resistance and systemic vascular resistance. The downsides are that it is a very potent vasodilator and can cause too much hypotension leading to increased vasopressor requirements. Another negative is that its half-life is long and takes 4-6 hours to reach a steady state. If milrinone causes too much hypotension or other side effects, it can take a long time to get out of the system. I use milrinone frequently, more so in non-ischemic cardiogenic shock.
2. Dobutamine causes less vasodilation and has a short half-life and results can be seen in minutes. This makes it more desirable early on in cardiogenic shock and I often will use dobutamine first line because of these two benefits over milrinone. It can cause more dysrhythmias than milrinone and since it is a beta-1 agonist, it can have decreased function if a patient is on beta blockers.
Inopressors: Epinephrine
1. Epinephrine is quick acting and works well in early vasoplegic cardiogenic shock. It has been shown in studies to worsen mortality and should be used in a limited capacity.
Vasopressors: Norepinephrine, Vasopressin
1. Norepinephrine is the vasopressor of choice. It will increase MAP and has some beta-1 contribution which can increase contractility and have minimal effect on the pulmonary vasculature.
2. Vasopressin is pure afterload for the LV but will lower pulmonary vascular resistance. It should only be used for isolated right heart failure or as an adjunct for norepinephrine to decrease norepinephrine requirements.
Phenylephrine and dopamine should not be used as vasopressors in cardiogenic shock patients. Phenylephrine is pure alpha and counterproductive to reduced systolic function. Phenylephrine also increases pulmonary pressures and makes the RV work harder. Dopamine causes arrhythmias and has minimal added benefit unless the cardiogenic shock is related to bradycardia. Norepinephrine was found to be superior to dopamine in a head-to-head study (SOAP II), especially in cardiogenic shock.
Table 1: Cardiogenic Shock Medications by Type
Cardiogenic Shock Subtypes:
A. Vasoplegic cardiogenic shock
Patients will have a low SVR even with a low cardiac output. This means they will need vasopressors to keep their MAP up but should be able to wean off as the vasoplegia improves.
Management: Inodilators + vasopressors
Due to the low cardiac output and low afterload these patients need inotropes and vasopressors. I think an Inopressor, epinephrine, can be used, but since this vasoplegia eventually wears off it makes more sense to use an Inodilator and vasopressor and wean the vasopressor off.
B. Hypotensive cardiogenic shock
This is the typical cardiogenic shock and the true phenotype for cardiogenic shock. The difference between hypotensive cardiogenic shock and vasoplegic cardiogenic shock is that vasoplegic cardiogenic shock is a blend of cardiogenic and distributive and hypotensive cardiogenic shock is only cardiogenic.
Management: Inodilators + vasopressors (only if necessary to maintain MAP)
If vasopressors are used in hypotensive non-vasoplegic cardiogenic shock, they can be counterproductive as they increase afterload in patients that already have a significantly elevated afterload and worsen cardiac output. In these situations, there are two options. One is to decrease the vasopressors and hope improvement in stroke volume will compensate for the drop in vasopressors or, if this does not occur, escalate to mechanical circulatory support.
C. Normotensive cardiogenic shock
Some would argue that a patient cannot be in cardiogenic shock if the patient is not hypotensive. This is probably true for other types of shock, but patients with severe cardiogenic shock can have such high afterload (clamped down) that they can maintain MAP without good cardiac output. These patients would have a severely reduced CI with decreased oxygen delivery leading to organ failure.
Management: Arteriodilators or Inodilators
These patients have the most options for management and the best outcomes. Afterload reduction is the best management for any patient in the congestive heart failure spectrum. If afterload reduction can be added it should be the first choice.
Table 2: Cardiogenic Shock Medications with Action and Subtype Use
How I Medically Manage Cardiogenic Shock:
A. Normotensive Cardiogenic Shock:
Is the diastolic BP higher than the MAP goal?
Yes 1. Nitroprusside
No 2. Milrinone/Dobutamine
I really like to use nitroprusside in this situation. It allows the heart to unload without increasing work on the heart. The dose is typically low and not at risk for cyanide toxicity. If the patient can reach CI goals with just arteriodilation then they can be transitioned to PO afterload reducers.
B. Hypotensive Cardiogenic Shock:
1. Milrinone/Dobutamine*
*try to avoid vasopressors, but MAP must be maintained
These patients are difficult and are the patients that are focused on in the cardiogenic shock protocols. They need cardiac rest and if they require inotropes and vasopressors, the vasopressors are working against the inotropes, and they need to be escalated to mechanical circulatory support.
C. Vasoplegic Cardiogenic Shock:
1. Dobutamine
2. Norepinephrine +/- Vasopressin
As stated above, you can consider epinephrine in this situation but I think epinephrine has its risks and prefer dobutamine. The reason I choose dobutamine is that it is fast on and fast off and if the patient does not tolerate the arteriodilation it can be stopped quickly. This also allows for easier removal of afterload when the vasoplegia resolves. Instead of weaning epinephrine to dobutamine or milrinone, the vasopressor can be weaned off and the inodilator left on.
Knowing the Limits of Medical Management
Cardiogenic shock has decreased oxygen supply and increased demand. Inotrope and vasopressor use in cardiogenic shock will increase supply but will also increase demand because it makes the heart work harder. The increase in contractility or the increase in afterload cause the heart to work harder and worsen oxygen consumption. If multiple inotropes and vasopressors are used, or they are at too high of a dose, it becomes more harmful than helpful.
Here is a figure showing the number of inotropes started before the initiation of mechanical circulatory support vs. survival. The survival was 68%, 46%, 35%, 35%, and 26% for patients requiring 0, 1, 2, 3, and 4 inotropes (5).
When should mechanical circulatory support be initiated?
A patient should be escalated to mechanical circulatory support when they need two or more inotropes/vasopressors to meet their MAP and CI goals. This is especially true for ischemic cardiogenic shock where cardiac rest is important. To help with escalating to mechanical circulatory support, I have included a table of the appropriate max dosing for inotropes and vasopressors.
Table 3: Inotrope/Vasopressor Dosing in Cardiogenic Shock
If the patient is unable to be supported with medical management alone then the decision for what type of mechanical support will begin.
The next post will discuss the possible mechanical circulatory support devices shown in table 4.
Table 4: Mechanical Circulatory Support Devices
REFERENCES:
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6. Levy B, Clere-Jehl R, Legras A, Morichau-Beauchant T, Leone M, Frederique G, et al. Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2018;72(2):173-82.
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10. Basir MB, Kapur NK, Patel K, Salam MA, Schreiber T, Kaki A, et al. Improved Outcomes Associated with the use of Shock Protocols: Updates from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv. 2019;93(7):1173-83.