Vasopressors

• Vasopressors are used for the treatment of hypotension and hemodynamic instability associated with shock.
• Vasopressor selection primarily depends on the etiology of hemodynamic instability.
• Norepinephrine is considered the initial vasopressor of choice for most adult patients in distributive/vasodilatory shock; epinephrine is considered first-line for anaphylactic shock.

Adrenergic vasopressors activate 3 types of receptors: 1) alpha-adrenergic, 2) beta-adrenergic, and 3) dopaminergic. Dopamine is the metabolic precursor of norepinephrine and displays dose-related receptor activity. At infusion rates of less than 5 mcg/kg/minute, dopamine targets dopaminergic receptors. At infusion rates of 5 to 10 mcg/kg/minute, it continues to stimulate dopaminergic receptors but also activates beta-receptors. At high doses, dopamine maintains beta activity while preferentially targeting alpha-receptors. Norepinephrine, the precursor of epinephrine, is much more selective in its targeting of alpha- and beta-receptors than dopamine and has no activity at dopaminergic receptors. Epinephrine is a potent nonselective alpha- and beta-agonist. Its beta effects predominate at lower doses, while alpha₁-mediated vasoconstriction predominates at high doses. Phenylephrine is a pure alpha₁-agonist, which increases blood pressure via peripheral vasoconstriction.[54335][65549][65550]

Non-adrenergic vasopressors include vasopressin and angiotensin II. Vasopressin causes potent peripheral vasoconstriction via vasopressin receptors located on vascular smooth muscle cells.[65549][65550] Angiotensin II causes vasoconstriction and increases the release of aldosterone.[62722]

Receptor Pharmacology of Vasopressors [62722][65549][65550]

*Dose listed for dose-related receptor activity only

Locations and Responses of Select Receptors[54335][65549][65550]

• Norepinephrine is the initial vasopressor of choice for most adult patients in distributive/vasodilatory shock and is an attractive option when attempting to increase systemic vascular resistance (SVR) and mean arterial pressure (MAP) with little change in heart rate.[65552][67037] It is recommended as the initial vasopressor of choice in septic shock.[67037]
• Dopamine is considered an alternative to norepinephrine in patients with septic shock in settings where norepinephrine is unavailable.[67037] It increases MAP and cardiac output, primarily due to an increase in stroke volume and heart rate.[43699][65552]
• Phenylephrine is a reasonable option in tachycardic patients in distributive/vasodilatory shock due to its lack of beta activity.[65552]
• Epinephrine is the vasopressor of choice in anaphylactic shock, as it provides beta₂ stimulation; it may also be added in cases of refractory hypotension.[65552][65559][67037] Epinephrine is the standard vasoactive drug used during cardiopulmonary resuscitation (CPR) for cardiac arrest.[66054]
• Vasopressin use is typically limited to adjunctive therapy in refractory shock.[65552][67037] Vasopressin offers no advantage as a substitute for epinephrine during cardiac arrest, and it is no longer recommended as a sole vasoactive drug during CPR.[66054]
• The mechanism of angiotensin II makes it a plausible treatment option to increase blood pressure and decrease catecholamine requirements in patients with refractory shock; however, comparative data is lacking.[62724]

• Data support the use of norepinephrine as a first-line vasopressor in the treatment of shock.
• There was no significant difference in mortality when comparing norepinephrine and dopamine as first-line vasopressors in the treatment of shock (n = 1,679); however, dopamine was associated with a higher rate of arrhythmias, including arrhythmias severe enough to require discontinuation of the study drug. Among patients with cardiogenic shock, mortality was significantly higher in the dopamine group.[43703]
• Comparison of norepinephrine to epinephrine in critically ill patients (n = 280) showed no significant difference in hemodynamic response or mortality but an increase in adverse effects (e.g., tachycardia, transient metabolic effects) associated with epinephrine.[65557]
• Large studies comparing vasopressin to other vasopressors in septic shock are lacking; data support a sparing effect on norepinephrine dose, but vasopressin use has not been shown to influence mortality.
• Low-dose vasopressin did not significantly reduce mortality in patients with septic shock (n = 778) when used in conjunction with norepinephrine compared with norepinephrine alone.[65555]
• Early use of vasopressin with hydrocortisone or placebo did not improve the number of kidney-failure free days or mortality rate when compared to norepinephrine (n = 409); however, there was less use of renal replacement therapy in the vasopressin group.[65556]
• Data do not support the use of vasopressin as a substitute for epinephrine in cardiac arrest.
• Repeated injections of standard-dose vasopressin or epinephrine during prolonged advanced cardiac life support resulted in comparable survival (n = 336).[65581]