What are vasopressors (Vasoconstrictor medications)?

From the Guidelines

Vasopressors are medications used to increase blood pressure in critically ill patients with hypotension or shock, with norepinephrine being the first-choice vasopressor, as recommended by the Surviving Sepsis Campaign guidelines 1. The primary vasopressors used in clinical practice are:

• Norepinephrine (first-line): Start at 0.1-0.5 mcg/kg/min, titrate to effect, as it has potent alpha-1 effects and minimal beta effects, making it suitable for most shock states 1.
• Epinephrine: Start at 0.05-0.5 mcg/kg/min, titrate as needed, and can be added to norepinephrine when an additional agent is needed to maintain adequate blood pressure 1.
• Vasopressin: Fixed dose of 0.03-0.04 units/min, can be added to norepinephrine with the intent of either raising mean arterial pressure or decreasing norepinephrine dosage 1.
• Phenylephrine: Start at 0.5-1 mcg/kg/min, titrate as needed, but is not recommended in the treatment of septic shock except in specific circumstances 1.
• Dopamine: Start at 5-10 mcg/kg/min, titrate up to 20 mcg/kg/min, and can be used as an alternative vasopressor agent to norepinephrine only in highly selected patients 1. When initiating vasopressors:

• Ensure adequate fluid resuscitation first
• Use a central venous catheter for administration
• Monitor blood pressure, heart rate, and urine output closely
• Titrate to achieve a mean arterial pressure (MAP) of 65 mmHg or higher, as recommended by the Surviving Sepsis Campaign guidelines 1. Vasopressors work by stimulating alpha-1 adrenergic receptors in blood vessels, causing vasoconstriction and increasing systemic vascular resistance, leading to improved blood pressure and organ perfusion. Choose the appropriate vasopressor based on the underlying cause of shock and patient-specific factors, and combine vasopressors or add inotropes if a single agent is insufficient to achieve hemodynamic goals, as suggested by the guidelines 1.

From the FDA Drug Label

Vasopressin causes vasoconstriction by binding to V1 receptors on vascular smooth muscle coupled to the Gq/11-phospholipase C-phosphatidyl-inositol-triphosphate pathway, resulting in the release of intracellular calcium. LEVOPHED functions as a peripheral vasoconstrictor (alpha-adrenergic action)

Vasopressors, also known as Vasoconstrictor medications, are drugs that cause vasoconstriction, or the narrowing of blood vessels. This effect is achieved through different mechanisms, such as:

• Binding to V1 receptors on vascular smooth muscle, as seen with vasopressin 2
• Alpha-adrenergic action, as seen with norepinephrine 3 These medications are used to increase systemic vascular resistance and mean arterial blood pressure, particularly in patients with vasodilatory shock.

From the Research

Definition and Purpose of Vasopressors

• Vasopressors, also known as vasoconstrictor medications, are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock 4.
• The primary objective of vasopressor therapy is to correct the vascular tone depression and improve organ perfusion pressure in septic shock-induced hypotension 5.
• Vasopressors bind to various receptors, including adrenergic, vasopressin, angiotensin II, and dopamine receptors, inducing vasoconstriction 4, 6.

Types and Choice of Vasopressors

• Norepinephrine is the first-choice vasopressor in septic and vasodilatory shock 4, 6, 5.
• Vasopressin and its analogues are considered second-line vasopressors 5.
• Other vasopressors, such as epinephrine, angiotensin II, and dopamine, may be used in specific situations or as adjunctive therapies 4, 6, 7.
• The choice and dose of vasopressors vary widely due to patient and physician practice heterogeneity 4, 6.

Adverse Effects and Limitations

• Vasopressor adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias 4, 6.
• No randomized controlled trials of vasopressors have shown a significant difference in 28-day mortality rate 4, 6, 8.
• Vasopressors should be administered simultaneously with fluid replacement to prevent and decrease duration of hypotension in shock with vasodilation 6.

Future Directions and Novel Vasopressors

• Predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge with fewer adverse effects 4, 6.
• New strategies, such as using multiple vasopressors with complementary mechanisms of action, may be developed to improve patient outcomes 6.
• Novel vasopressor agents, such as synthetic human angiotensin II, may increase blood pressure and reduce the need for high doses of catecholamine vasopressors in severe or refractory vasodilatory shock 7.