What are vasopressors?

What Are Vasopressors?

Vasopressors are medications that induce vasoconstriction to increase blood pressure and restore adequate tissue perfusion in patients with shock states, primarily by activating adrenergic, vasopressin, or angiotensin receptors on vascular smooth muscle. 1

Classification and Mechanisms of Action

Vasopressors are categorized into three main classes based on their receptor targets 1:

Sympathomimetic Agents (Catecholamines)

• Direct-acting catecholamines work by stimulating α (alpha) and β (beta) adrenergic receptors on vascular smooth muscle and cardiac tissue 1
• α-receptor stimulation causes arterial and venous vasoconstriction, increasing systemic vascular resistance and mean arterial pressure 1
• β-receptor stimulation increases cardiac inotropy (contractility) and heart rate, with β2 receptors also decreasing venous resistance 1
• Common agents include norepinephrine (predominantly α with some β activity), epinephrine (mixed α and β), dopamine (dose-dependent receptor activity), and phenylephrine (pure α-agonist) 1

Vasopressin Analogues

• Vasopressin is a nonapeptide hormone that acts through V1a receptors to cause catecholamine-independent vasoconstriction 1
• This mechanism is particularly valuable in septic shock where α-adrenergic receptor down-regulation may occur 1
• Vasopressin also stimulates V2 receptors (anti-diuretic effects) and paradoxically induces nitric oxide synthesis, which may preserve renal perfusion 1
• Typical dosing is 0.01-0.04 units/min in adults 1 and up to 0.03 units/min in hemorrhagic shock 2

Angiotensin II

• Angiotensin II acts on AG1 and AG2 receptors to produce vasoconstriction through a distinct mechanism from catecholamines 1
• May be useful in profoundly hypotensive patients refractory to other vasopressors 3

Clinical Applications by Shock Type

Septic and Vasodilatory Shock

• Norepinephrine is the first-line vasopressor after adequate fluid resuscitation in septic shock 1, 3
• Vasopressin (0.01-0.04 units/min) can be added to decrease norepinephrine requirements, though it has not shown mortality benefit 1, 3
• Epinephrine may be added in norepinephrine-refractory patients 1, 3

Hemorrhagic Shock

• Vasopressors should only be used transiently in life-threatening hypotension (systolic BP <80 mmHg) after volume resuscitation has been initiated 1, 2
• Norepinephrine is recommended as the first-line agent if restricted volume replacement fails to achieve target blood pressure (systolic 80-90 mmHg) 1, 2
• The primary treatment remains volume restoration and hemorrhage control, not vasopressor support 2
• Low-dose vasopressin (bolus of 4 IU followed by 0.04 IU/min) may decrease blood product requirements 1

Cardiogenic Shock

• Norepinephrine remains appropriate as first-line vasopressor when arterial pressure is inadequate 1, 4
• Inotropic agents (dobutamine, milrinone) must be added if myocardial dysfunction is present, as vasopressors alone may worsen cardiac output by increasing afterload 1
• Dopamine at higher doses (>5 μg/kg/min) provides vasopressor effects but has more adverse effects than norepinephrine and should be restricted to bradycardic patients 1, 3

Critical Monitoring and Safety Considerations

Hemodynamic Targets

• Target mean arterial pressure (MAP) ≥65 mmHg to ensure adequate organ perfusion 2
• In hemorrhagic shock with permissive hypotension strategy, target systolic BP 80-90 mmHg until bleeding is controlled 1
• MAP targets may need individualization based on baseline blood pressure and comorbidities 2

Essential Monitoring Parameters

• Urine output (target >0.5 mL/kg/hour) and lactate clearance as markers of tissue perfusion 2
• Cardiac function assessment is mandatory before vasopressor initiation, as increased afterload can worsen outcomes in myocardial dysfunction 1
• Vasopressors have a narrow therapeutic window and require precise titration with close monitoring 2

Common Pitfalls and Adverse Effects

• Excessive vasoconstriction can cause organ ischemia, infarction, and worsened microcirculatory flow 1, 3
• Other adverse effects include hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias 3, 5
• Early vasopressor use in hemorrhagic shock may be harmful if used before adequate volume resuscitation or when systolic BP >80 mmHg 1
• Vasopressors should be withdrawn as soon as clinically feasible 2

Receptor Pharmacology Summary

The physiologic response to vasopressors follows a sigmoidal dose-response curve rather than a linear relationship, with increasing doses producing a pharmacologic response followed by a plateau effect 1. Understanding receptor selectivity is crucial:

• α1-receptors: Arterial vasoconstriction, increased afterload 1
• α2-receptors: Venous vasoconstriction, increased preload 1
• β1-receptors: Increased inotropy and heart rate 1
• β2-receptors: Vasodilation, decreased venous resistance 1
• V1a-receptors: Catecholamine-independent vasoconstriction 1
• Dopamine receptors: Renal and splanchnic vasodilation at low doses 1