What are vasoactive substances and what are they used for?

2 de March de 20243 de March de 2024 Grupo NAVE

By: Ana Paula Mazzarella, Felipe Costa, and Adriano Carregaro

The need for vasoactive drugs is common in various anesthetic procedures. But after all, how do these drugs act in the body? Do they all have the same function?

It is widely known that anesthesia affects the cardiovascular system, typically causing a reduction in cardiac output. This complication occurs because the anesthetic can reduce cardiac contractility (negative inotropy), decrease heart rate, or even systemic peripheral resistance. One of the final effects of this process can be a drop in blood pressure, known as hypotension.

In addition to anesthesia, other factors can cause hypotension, such as surgical procedures with excessive blood loss or comorbidities present in the patient, including dehydration, heart problems, and various infections.

The approach to treating hypotension during the perioperative period should begin before even choosing which vasoactive agent to use. In this case, we should adjust the patient's anesthetic plan, reducing the impact of these medications on cardiovascular parameters. We should also ensure that volume replacement is sufficient, paying special attention to cases of dehydration. In situations where these measures do not resolve the issue, it is necessary to initiate treatment through the use of vasoactive agents.

Vasoactive agents are divided into inotropes (cardiac effects), vasopressors, and vasodilators (vascular effects), acting on adrenergic receptors regulated by the sympathetic nervous system.

Adrenergic Receptors	Effects
α1	Post-synaptic, vasoconstriction, and increased peripheral resistance
α2	Pre-synaptic, release of norepinephrine
𝛽1	Post-synaptic, tachycardia, and increased myocardial contractility
𝛽2	Post-synaptic, vasodilation, and decreased peripheral resistance

Non-selective vasoactive agents

Non-selective agonists are drugs that have selectivity for more than one type of receptor. In this class, the following are included:

Dopamine

Dopamine acts by increasing the activity of the sympathetic nervous system, resulting in greater release of norepinephrine, causing an increase in blood pressure and myocardial contractility. Its action occurs on both alpha and beta receptors, but depending on the dose, there is greater stimulation of one over the other.

This drug is considered dose-dependent, meaning its effect is related to the dose used. Doses between 5 and 7 μg/kg/min activate beta-adrenergic receptors, increasing myocardial contractility. Higher doses, between 10 and 20 μg/kg/min, activate alpha-adrenergic receptors, promoting peripheral vasoconstriction and increasing systemic vascular resistance, thus raising blood pressure.

Dobutamine

Dobutamine is an inotropic agent with high selectivity for beta1 receptors, significantly increasing myocardial contractility. Its use is also through continuous infusion at rates ranging from 1 to 20 μg/kg/min, and it is indicated in cardiomyopathies affecting myocardial contractility. This medication has little affinity for alpha receptors.

Ephedrine

Ephedrine acts on all adrenergic receptors, promoting tachycardia and increasing blood pressure through peripheral vasoconstriction. However, it also acts on presynaptic receptors, stimulating the release of norepinephrine, intensifying this effect. Its use is typically administered as a bolus of 0.1 to 0.2 mg/kg; therefore, it is usually used when short-duration effects are desired.

Norepinephrine/Noradrenaline

Norepinephrine is an important vasopressor, increasing vascular resistance and consequently blood pressure, which can help improve blood perfusion and oxygenation of organs and tissues in the body. This often occurs due to intense stimulation of alpha-adrenergic receptors.

Its use is indicated in cases of hypotension refractory to volume replacement maneuvers, such as in patients with sepsis. However, norepinephrine has some adverse effects, depending on the dose, such as reflex bradycardia due to a considerable increase in peripheral vascular resistance, and pronounced renal, mesenteric, and cutaneous vasoconstriction.

Epinephrine/Adrenaline

Epinephrine, or adrenaline, is used only as a last resort. Its action is predominantly on alpha-adrenergic receptors, causing intense peripheral vasoconstriction. The vasoconstriction is so intense that it significantly reduces peripheral perfusion and splanchnic organ perfusion, prioritizing the mobilization of intravascular volume to the central compartment. Its use is most indicated in cases of cardiac arrest, starting with a bolus of 0.01 mg/kg, between two and three cycles of cardiopulmonary resuscitation, and if unresponsive, the dose can be increased to 0.1 mg/kg.

Selective Agonists

Vasopressin

Vasopressin, also known as antidiuretic hormone (ADH), is released endogenously in physiological stress situations. Its use is indicated for patients with sepsis not responsive to norepinephrine. It acts on V1 receptors, abundant in blood vessels and responsible for the vasoconstriction effect, optimizing blood pressure by improving microcirculation.

It also acts on V2 receptors, promoting an antidiuretic effect, and on V3 receptors, present in the pituitary gland, responsible for the release of adrenocorticotropic hormone. Its use is through continuous infusion, starting with a rate of 0.001 IU/kg/min and titrating the infusion up to a maximum dose of 0.004 IU/kg/min.

Phenylephrine

Phenylephrine has selectivity only for alpha-1 receptors, causing vasoconstriction. However, its use in hypotensive situations is a last resort, due to its intense peripheral vasoconstriction and reduction in cardiac output, promoting significant adverse effects on the perfusion of essential organs such as the kidneys.

Esmolol

Although this post is focused on the use of vasoactive agents for the treatment of hypotension, it's worth noting that there are other vasoactive agents that may have different effects. Esmolol is one of them. It is a beta-adrenergic blocker indicated for patients with systemic hypertension where reducing heart rate is desirable, especially in patients with ventricular tachycardia refractory to treatment with lidocaine. It is administered as a bolus of 0.5 mg/kg followed by continuous infusion at a rate between 50 and 200 μg/kg/min.

Vasodilators

Vasodilators are rarely used in veterinary medicine, but their important mention within the classification of vasoactive drugs should not be overlooked. Their use is limited to very specific and delicate procedures involving patients needing cardiac surgery or experiencing hypertensive crises associated with pulmonary hypertension.

Sodium Nitroprusside

Sodium nitroprusside promotes vasodilation, reducing afterload; thus, it can increase cardiac output in some situations. Its use is indicated when rapid reduction of blood pressure is necessary, especially in delicate cardiac surgical procedures and hypertensive emergencies associated with pulmonary hypertension.

Nitroglycerin

Like nitroprusside, nitroglycerin is also a vasodilator used in cases of hypertensive crises and in patients with heart failure. Its mechanism of action, similar to that of nitroprusside, is related to its conversion to nitric oxide (NO), a molecule that plays an important role in the regulation of vascular tone, causing relaxation of vascular smooth muscles, leading to vasodilation.

So...

As we have seen, vasoactive drugs are much more than mere medications that increase blood pressure. They are not all the same, and what sets them apart is the mechanism of action and intensity with which they bind to each receptor. Therefore, it is important to identify the cause in order to make the appropriate choice of vasoactive drug, thereby avoiding unwanted effects on tissue perfusion unnecessarily.

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Find out more:

Humm et al. Use of sodium nitroprusside in the anaesthetic protocol of a patent ductus arteriosus ligation in a dog. Vet J, 173:194-196, 2007.
Scroggin Jr et al. The use of vasopressin for treating vasodilatory shock and cardiopulmonary arrest. J Vet Emerg Crit Care, 19:145-157, 2009.
Silverstein et. Controversies regarding choice of vasopressor therapy for management of septic shock in animals. J Vet Emerg Crit Care, 25:48-54, 2015.
Murphy et al. Use of vasopressors for treatment of vasodilatory hypotension in dogs and cats by Diplomates of the American College of Veterinary Emergency and Critical Care. J Vet Emerg Crit Care, 32:714-722, 2022.

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