Mount Sinai Expert Guides. Группа авторов
receptors and mechanisms of action.An example of this principle is the use of a pure alpha‐adrenergic agonist such as phenylephrine for hypotension resulting from cardiogenic shock. It might seem intuitive to use such a drug to improve hypotension from inadequately contracting the left ventricle. However, understanding the effect of such a drug on the hemodynamic equations noted above will allow you to conclude that phenylephrine use would be counterproductive. It would lead to decreased stroke volume from an increased afterload on the weakened left ventricle without the benefit of inotropic support.
Most vasoactive drugs act on multiple receptors, and many agents activate different receptors depending on the dose administered:The best example of this is dopamine, which preferentially stimulates β‐1 receptors at low doses and α receptors at higher doses.Similarly, dobutamine can increase myocardial contractility by stimulating β‐1 receptors. However, it can cause vasodilation by simultaneous activation of β‐2 receptors.The principle is to understand that vasoactive medications can have mixed hemodynamic effects, and often have different responses based on dose.
A given vasoactive agent can have both direct actions and reflex actions:The vascular system is closely regulated by multiple physiologic mechanisms including the autonomic nervous system that seeks to ensure cardiovascular stability.For example, phenylephrine‐induced vasoconstriction can lead to increased mean arterial pressure, which may lead to baroreceptor activation and a compensatory reflex bradycardia.
Responsiveness to the vasoactive medications can decrease over time due to a phenomenon known as tachyphylaxis:Up‐titration of doses or initiation of new agents with different receptor targets must be done regularly.
Central line access and arterial line monitoring are a must:Catecholamines and vasopressor agents are given as continuous infusions due to their short half‐lives. They carry significant risks of peripheral extremity ischemia due to potent vasoconstriction as well as skin necrosis if they extravasate. Central venous access is usually necessary.With all intravenous vasoactive infusions, invasive hemodynamic monitoring with an arterial line is needed because of rapid hemodynamic changes and side effects such as arrhythmias
Vasoactive medications in focus
| Epinephrine | |
| Receptor binding | α‐1, β‐1, β‐2 |
| Pharmacology | β receptor predominant at lower doses, α receptor predominant at higher doses |
| Dosing range | 0.01–0.10 μg/kg/min (for 70 kg adult, that is 0.7–7 μg/min) |
| Clinical scenarios to consider use | Cardiac arrest Extreme hemodynamic collapse Additional agent when already on several vasopressors Shock after cardiac surgery Right ventricular failure Anaphylaxis |
| Clinical pearls | Reserved for refractory or severe shock despite multiple vasopressors or extreme hemodynamic compromise Associated with decreased mesenteric, coronary, and renal blood flow and regional ischemia resulting in a lactic acidosis |
| Norepinephrine | |
| Receptor binding | α‐1, β‐1, β‐2 |
| Pharmacology | Less β receptor activity than epinephrine α receptor predominant at higher doses |
| Dosing range | 0.01–3 μg/kg/min (for 70 kg adult, that is 0.7–210 μg/min) |
| Clinical scenarios to consider use | Septic shock (first line) Cardiogenic shock (first line) Vasoplegia after cardiac surgery |
| Clinical pearls | If norepinephrine requirements are increasing, evaluate volume status and pH Norepinephrine has been demonstrated to be equivalent to other vasopressor agents, including dopamine, with less adverse events, including tachyarrhythmias In cardiogenic shock, mortality was lower with norepinephrine than with dopamine. This has led to use of norepinephrine as first line agent for cardiogenic shock, including shock from an acute myocardial infarction The Surviving Sepsis Campaign guidelines recommend norepinephrine as the first line agent for septic shock |
| Dopamine | |
| Receptor binding | α‐1, β‐1, β‐2, D1 |
| Pharmacology | Binds DA receptors at low doses, promoting vasodilation particularly in the splanchnic circulation Binds adrenergic receptors at higher doses, leading to vasoconstriction |
| Dosing range | 0.5–3 μg/kg/min, predominantly D1 agonism 3–10 μg/kg/min, weak β‐1 agonism; promotes norepinephrine release >10 μg/kg/min, increasing α‐1 receptor agonism: Vasodilation of capillary beds (low dose)Increased contractility and chronotropy (medium dose)Vasoconstriction (high dose) |
| Clinical scenarios to consider use | Cardiogenic shock complicating acute myocardial infarction with moderate hypotension(SBP 70–100 mmHg); however, this has largely been replaced by norepinephrine Symptomatic bradycardia (temporizing measure) |
| Clinical pearls | While often used as a vasopressor agent that can be used peripherally while central access is being set up, extravasation of dopamine is not benign Renal dosing of dopamine for acute kidney injury was hypothesized to be of use due to vasodilation and improved blood flow to the splanchnic circulation at lower doses (1–3 μg/kg). However, clinical trials have not shown a benefit and it is currently not recommended for this use |
| Dobutamine | |
| Receptor binding | β‐1, β‐2, minor α‐1 |
| Pharmacology | Synthetic catecholamine with preferential β‐1 agonism (3:1 ratio of β‐1 to β‐2), inotropic effect β‐2 activity causes vasodilation, which makes dobutamine an inodilator Progressive α‐1 agonism at high doses causes vasoconstriction |
| Dosing range | 2–40 μg/kg/min Dose in ICU for cardiogenic shock rarely exceeds 10 μg/kg/min |
| Clinical scenarios to consider use | Acute decompensated systolic heart failure Refractory septic shock associated with low cardiac output (also known as ‘hypodynamic’ or ‘cold’ sepsis, a relatively small subset of patients) Pharmacologic stress testing (e.g. for ischemia, viability, aortic stenosis severity) |
| Clinical pearls |
Tolerance develops after a few days of therapy Ventricular arrhythmias can occur at any dose Dobutamine significantly increases myocardial oxygen demand so do not use in patients with acute coronary syndromes, severe and unstable coronary disease, or ongoing ischemia Dobutamine has inotropic properties that increase myocardial contractility and cardiac output, while the vasodilatory effects further improve cardiac output by reducing afterload. This makes dobutamine an ideal agent in decompensated |