12: Vasoactive Drugs

Vasoactive Drugs

Ajay S. Vaidya1 and Umesh K. Gidwani2

1 Keck School of Medicine of USC, Los Angeles, CA, USA

2 Icahn School of Medicine at Mount Sinai, New York, NY, USA


  • The purpose of vasoactive drugs in the ICU is to improve the mean arterial pressure (MAP) and cardiac output (CO) by affecting left ventricular contractility, volume status, and systemic vascular resistance (SVR). Vasopressors are generally indicated in the setting of circulatory shock. MAP is related to CO and SVR by the equation:


  • Cardiac output is the volume of blood the heart is able to pump through the circulatory system per minute. The resistance to blood flow due to the entire systemic vasculature is known as the systemic vascular resistance, and is primarily a function of vascular smooth muscle tone. CO is directly related to heart rate (HR) and stroke volume (SV) as seen by the equation:


  • Stroke volume is a function of left ventricular end‐diastolic filling pressure (preload), the resistance against which the ventricle has to eject blood during systole (afterload), and the intrinsic ability of the cardiac muscle to contract (contractility). Each of these hemodynamic factors needs to be interrogated to find the reason for circulatory shock, and will be critical in understanding how to tailor therapy to the patient’s physiology.

Basic properties

  • Vasopressors are agents that increase blood pressure by causing vasoconstriction (SVR) through the activation of various receptor targets.
  • Inotropes are agents that augment stroke volume, and thus cardiac output, by increasing myocardial contractility.
  • Inodilators are agents with inotropic properties, but also with vasodilatory effects.
  • It is important to note that some vasoactive agents have mixed actions, as they can exert effects on multiple receptor targets.


  • Vasopressors and inotropes are typically used in the ICU to support the blood pressure during circulatory shock and improve end‐organ perfusion.
  • Vasodilators and venodilators are used to lower SVR and blood pressure, or to reduce filling of the heart.

Types of shock

  • There are four different types of shock: cardiogenic, distributive, hypovolemic, and obstructive. Mixed forms of shock can also occur.
  • Table 12.1 shows the typical hemodynamic changes seen with each type of shock, but individual clinical situations often involve more complicated physiologic determinations.

Table 12.1 Different forms of shock states.

Cardiac output Heart rate Stroke volume Systemic vascular resistance Venous pressure(PCWP/CVP)
Cardiogenic An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing upwards.
Distributive (i.e. sepsis, anaphylaxis, neurogenic shock) An illustration of an arrow pointing upwards.
(occasionally impaired)
An illustration of an arrow pointing upwards. An illustration of an arrow pointing upwards.
(occasionally decreased)
An illustration of an arrow pointing downwards. Normal or
An illustration of an arrow pointing downwards.
Hypovolemic An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards.
Obstructive(i.e. pulmonary embolus, pericardial tamponade, tension pneumothorax) An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. Normal or
An illustration of an arrow pointing downwards.
(increased inpericardial tamponade)
Mixed An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards. An illustration of an arrow pointing downwards. An illustration of an arrow pointing upwards.

Selecting vasoactive therapy

It is critical to understand the physiology of the shock that you are treating, and the receptor targets for each vasoactive medication, so that you can tailor therapy to the particular clinical situation.

Low preload (LVEDP)

  • In distributive, obstructive, or hypovolemic shock, proper fluid resuscitation is critical to improving blood pressure, cardiac output, and end‐organ perfusion. Monitoring of hemodynamic parameters and filling pressures can be helpful in this setting.
  • In mixed shock states, invasive hemodynamic monitoring can be useful in determining the predominant mechanism of shock and to customize therapy to the physiology of the patient.

Receptors affected by vasoactive medications

  • Vasoactive medications often work as agonists or antagonists of adrenergic or parasympathetic receptors. These selected receptors represent the principal targets for vasoactive therapy in the intensive care setting (Table 12.2).

Key principles of vasoactive medication use

  • Diagnose and understand mechanism causing hypotension:
  • Physical examination, urine output, laboratory testing, imaging, and invasive hemodynamic monitoring can be important tools to differentiate the nature of the patient’s shock.
  • Dosage and selection of medication should be titrated to achieve a blood pressure sufficient to maintain end‐organ perfusion, as evidenced by metrics such as mentation, urine output, and blood lactate levels.
  • Critically ill patients also require frequent re‐evaluation for further hemodynamic insults, response to therapy, or side effects that may require changes in therapeutic strategy.

    Table 12.2 Action of vasoactive medications.

    Receptor Location Action
    α‐1 adrenergic Vascular smooth muscle (peripheral, renal, coronary) Systemic vasoconstriction – increased SVR
    α‐2 adrenergic Vascular smooth muscle and central nervous system Vasodilation – decreased SVR
    β‐1 adrenergic Cardiac muscle Increased heart rate (chronotropy) and contractility (inotropy)
    Increased cardiac output
    Minimal vasoconstriction
    β‐2 adrenergic Vascular smooth muscle (peripheral and renal) Vasodilation
    Reduced SVR
    Dopamine (D1) Vascular smooth muscle (peripheral, renal, splanchnic, coronary, cerebral) Vasodilation in capillary beds
    Acetylcholine (ACh) Parasympathetic nervous system (heart, sinoatrial and atrioventricular nodes, GI tract, eyes) Has chronotropic effects on heart
    Atropine is an antagonist of muscarinic ACh receptors
    Atropine can stimulate or accelerate AV node conduction
    Phosphodiesterase 3 (PDE‐3) Cardiac muscle and vascular smooth muscle Increased contractility (inotropy) and improves diastolic relaxation (lusitropy)
    Vasopressin (V1, V2) Vascular smooth muscle and renal collecting duct V1 – stimulation causes vasoconstriction
    V2 – mediate water reabsorption in renal collecting system

  • Tailor vasoactive therapy to correct the specific hemodynamic derangements underlying the hypotension:

    • This requires understanding adrenergic 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

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
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

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

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

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 heart failure. Remember to use an agent such as norepinephrine as the initial agent if shock and hypotension are present

Receptor binding PDE‐3
Pharmacology PDE‐3 inhibitor
PDE‐3 inhibition increases intracellular cAMP concentrations, enhancing contractility and promoting vascular smooth muscle relaxation
Relatively long half‐life (2–4 hours)
Renal elimination
Dosing range 0.125–0.75 μg/kg/min (renal adjust)
Clinical scenarios to consider use Acute decompensated systolic heart failure
Right ventricular failure
Clinical pearls Fewer arrhythmogenic and chronotropic side effects compared with catecholamines, but vasodilatory effects can worsen hypotension that limits the use of milrinone in patients with shock
Can be useful if adrenergic receptors are downregulated or desensitized in setting of chronic heart failure, or after chronic β‐agonist administration
Potent pulmonary vasodilator so can be useful in right ventricular (RV) failure by lowering pulmonary vascular resistance (RV afterload)
Long half‐life (2–4 hours); hypotension can persist for longer so short‐term infusions may be more beneficial than continuous infusions

Receptor binding α‐1
Pharmacology Pure α‐1 agonism
Minimal inotropic and chronotropic effect
Rapid onset, short half‐life
Dosing range 0.4–9.1 μg/kg/min (for 70 kg adult, that is 28–637 μg/min)
Bolus administration possible, usually 0.1–0.5 mg every 5–15 minutes
Clinical scenarios to consider it Dynamic intracavitary gradient: ‘suicide ventricle’ after transcatheter aortic valve replacement (TAVR), anteroapical STEMI, hypertrophic cardiomyopathy with systolic anterior motion of the mitral valve and LV outflow obstruction, and Takotsubo cardiomyopathy
Inadvertent combination of sildenafil and nitrates
Hypotension during PCI or anesthesia‐related hypotension
Hypotension in the setting of atrial fibrillation with rapid ventricular rate
Aortic stenosis with hypotension
Vagally mediated hypotension during percutaneous diagnostic or therapeutic procedures
Clincial pearls Phenylephrine increases MAP by raising SVR (afterload), and therefore is particularly useful when SVR <700 dyn·s/cm5
Increased afterload can result in decreased stroke volume and cardiac output in patients with pre‐existing cardiac dysfunction

Contraindicated in patients with SVR >1200 dyn·s/cm5, which is most patients with cardiogenic shock
Lower concentration (20 μg/mL) available which can be infused peripherally while awaiting central line placement
Generally not recommended for septic shock unless serious arrhythmias happen with norepinephrine
Can cause reflex bradycardia

Receptor binding V1, V2
Pharmacology Agonism of V1 receptors on smooth muscle causes vasoconstriction
Agonism of V2 receptors in nephron induces translocation of aquaporin water channels to plasma membrane of collecting duct cells
Dosing range Fixed dose: 0.04 units/min
Clinical scenarios to consider it When avoiding β agonism is desired (e.g. left ventricular outflow obstruction, tachyarrhythmia) or when trying to reduce dose of first line agent
Hypotension accompanied by severe acidosis
Second line agent in refractory vasodilatory/septic shock
Clinical pearls Vasoconstrictive effect is relatively preserved despite conditions of hypoxia and acidosis (which can attenuate effects of catecholamines)
Doses above 0.04 units/min have been associated with coronary and mesenteric ischemia and skin necrosis
Rebound hypotension often occurs after withdrawal of vasopressin. To avoid this, the dose is slowly tapered by 0.01 units/min every 30 minutes

Reading list

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Nov 20, 2022 | Posted by in ANESTHESIA | Comments Off on 12: Vasoactive Drugs

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