What are vasopressors?

What Are Vasopressors?

Vasopressors are medications that cause vasoconstriction through receptor-mediated pathways to increase blood pressure, primarily used in critically ill patients with shock who remain hypotensive despite adequate fluid resuscitation. 1

Mechanism of Action

Vasopressors work through distinct receptor systems to achieve vasoconstriction and blood pressure elevation:

Catecholamine-Based Vasopressors

• Direct-acting catecholamines (norepinephrine, epinephrine, phenylephrine, dopamine) stimulate α and β receptors on vascular smooth muscle and cardiac tissue, producing both vasoconstriction and increased cardiac contractility. 1
• α-adrenergic stimulation increases arterial resistance and cardiac afterload through arterial vasoconstriction, while also causing venoconstriction particularly in the splanchnic circulation, which actively shifts blood volume from capacitance vessels to the systemic circulation. 2, 1
• β-adrenergic stimulation directly increases myocardial contractility and heart rate, while β2-receptor activation decreases venous resistance and increases venous return. 1

Non-Catecholamine Vasopressors

• Vasopressin activates V1a receptors to produce catecholamine-independent vasoconstriction, which is particularly useful when α-adrenergic receptors are down-regulated in conditions like septic shock. 1
• Angiotensin II activates AG1 and AG2 receptors to substantially increase systemic vascular resistance without altering cardiac output, thereby increasing blood pressure. 1

Specific Vasopressor Agents

Norepinephrine

• Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation, recommended by multiple critical care societies. 2, 3, 4
• Norepinephrine induces both arterial and venous α-adrenergic stimulation, causing venoconstriction that increases pressure in capacitance vessels and shifts splanchnic blood volume to systemic circulation. 1
• Infusion rates typically range from 0.2–1.0 μg/kg/min for hemodynamic support. 2

Vasopressin

• Vasopressin is a polypeptide hormone available as 20 units/mL for intravenous administration after dilution. 5
• Low-dose vasopressin (up to 0.03-0.04 IU/min) can be added to reduce norepinephrine requirements in patients with refractory shock. 2, 6
• Vasopressin deficiency develops in early septic shock due to depletion of stores and inadequate synthesis, making supplementation physiologically rational. 1

Epinephrine

• Epinephrine is equipotent to norepinephrine regarding systemic blood pressure and vascular resistance effects, though low doses may lower blood pressure via β2-receptor activation. 1
• Dosing ranges from 0.05–0.5 μg/kg/min for continuous infusion, with 1 mg boluses during resuscitation repeated every 3-5 minutes. 2

Dopamine

• Dopamine at high doses (>5 μg/kg/min) stimulates α-adrenergic receptors and acts as a vasopressor, while lower doses (3-5 μg/kg/min) provide inotropic effects. 2
• Dopamine is associated with more side effects and potentially higher mortality compared to norepinephrine, and should be restricted to bradycardic patients. 2, 3

Phenylephrine

• Phenylephrine is a pure α1-adrenergic agonist with no β-adrenergic activity, causing vasoconstriction without direct inotropic effects. 1
• Phenylephrine may improve blood pressure but reduce blood flow through increased systemic vascular resistance, potentially compromising microcirculatory flow. 1

Clinical Applications

Septic and Vasodilatory Shock

• Norepinephrine is recommended as the agent of choice for vasodilatory shock, including septic shock, after fluid resuscitation fails to restore adequate blood pressure. 2, 3
• Vasopressors should be administered to maintain target arterial pressure when fluid therapy alone is insufficient. 2

Hemorrhagic and Trauma Shock

• In hemorrhagic shock, vasopressors should be used transiently only in the presence of life-threatening hypotension (systolic BP <80 mmHg) after restricted volume replacement. 2, 6
• Norepinephrine is the first-line vasopressor after adequate fluid resuscitation in trauma patients, with a mean arterial pressure target of ≥65 mmHg. 6
• The pathophysiology of acute blood loss involves an initial vasoconstriction phase followed by a vasodilatory, sympathoinhibitory phase, which may benefit from vasopressor support to counteract vasodilation. 2

Cardiac Dysfunction

• Dobutamine infusion (2-20 μg/kg/min) is recommended in the presence of myocardial dysfunction, as vasopressors may increase cardiac afterload and impair ventricular function. 2

Hemodynamic Effects and Monitoring

Beneficial Effects

• Norepinephrine decreases preload dependency by increasing venous return via a shift of unstressed to stressed volume, with subsequent transient increase in cardiac output. 1
• Vasopressors restore mean arterial pressure and systemic blood flow to prevent regional hypoperfusion and tissue hypoxia. 2

Adverse Effects

• Vasopressors may increase cardiac afterload if infusion rate is excessive or left ventricular function is impaired, requiring assessment of cardiac function. 2, 1
• Excessive vasoconstriction can compromise microcirculatory flow and lead to organ ischemia, particularly with pure α-agonists. 1, 3
• Other adverse effects include hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. 3, 4

Monitoring Requirements

• Urine output should be monitored with a target of >0.5 mL/kg/hour, and lactate clearance should be assessed as a marker of improved tissue perfusion. 6
• Vasopressors have a narrow therapeutic spectrum and require precise therapeutic targets, close monitoring, and should be withdrawn as soon as possible. 6

Important Clinical Pitfalls

• Receptor responses follow sigmoidal curves rather than linear relationships, resulting in pharmacological response to increasing doses followed by a plateau effect. 1
• Prolonged catecholamine exposure causes α-adrenergic receptor down-regulation in septic shock, reducing responsiveness and necessitating alternative vasopressor mechanisms. 1
• Vasopressors should not be used to achieve systolic blood pressure targets of 80-90 mmHg in early trauma resuscitation if permissive hypotension and restricted volume replacement can achieve these targets, as premature vasopressor use may worsen outcomes. 2
• In acute heart failure, vasopressors should be avoided in patients with systolic blood pressure <90 mmHg or symptomatic hypotension, and used with caution in significant mitral or aortic stenosis. 2