Vasopressors

Vasopressors are a pharmacological class of drugs used to elevate arterial blood pressure in critically ill patients with hypotension, primarily due to shock. These agents exert their therapeutic effect by vasoconstricting blood vessels, increasing systemic vascular resistance (SVR), and often enhancing cardiac output (CO) or inotropy depending on the specific agent used.

Vasopressors are essential in the management of life-threatening shock states, including septic shock, cardiogenic shock, neurogenic shock, and anaphylactic shock, where restoring adequate organ perfusion and mean arterial pressure (MAP ≥ 65 mmHg) is critical. These drugs are administered via continuous intravenous infusion, most commonly in intensive care unit (ICU) or emergency settings.

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Pathophysiological Basis

Shock states involve inadequate tissue perfusion due to circulatory failure. The body’s natural compensatory mechanisms often fail to maintain adequate blood pressure and perfusion. Vasopressors intervene by:

• Stimulating adrenergic receptors (α1, β1, β2): Leading to vasoconstriction, increased heart rate, and myocardial contractility

• Stimulating vasopressin (V1) receptors: Promoting non-adrenergic vasoconstriction

• Augmenting dopaminergic receptors (D1, D2): Improving renal perfusion at low doses

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Classification of Vasopressors by Mechanism of Action

1. Catecholamines

   • Act primarily on adrenergic receptors

   • Examples: Norepinephrine, Epinephrine, Dopamine, Dobutamine (inotrope with vasopressor effect)

2. Non-Catecholamine Adrenergic Agonists

   • Selective α1 agonists

   • Example: Phenylephrine

3. Non-Adrenergic Vasopressors

   • Act on vasopressin (V1) receptors

   • Example: Vasopressin (ADH), Terlipressin (synthetic analog)

4. Synthetic Angiotensin II

   • Acts via angiotensin II type 1 receptor

   • Example: Giapreza® (Angiotensin II)

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Generic Names and Mechanisms of Action

1. Norepinephrine (Noradrenaline)

• Mechanism: Potent α1 and β1 agonist → peripheral vasoconstriction + modest inotropy

• Indication: First-line vasopressor in septic shock

• Route: IV infusion (central line preferred)

• Effects:

  • ↑ SVR, ↑ MAP

  • Mild ↑ heart rate

• Brand: Levophed®

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2. Epinephrine (Adrenaline)

• Mechanism: Potent α1, β1, and β2 agonist → vasoconstriction + inotropy + bronchodilation

• Indication:

  • Anaphylactic shock

  • Cardiac arrest (ACLS protocol)

  • Septic shock (second-line)

• Route: IV infusion, IM (anaphylaxis), IV push (cardiac arrest)

• Brand: Adrenalin®

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3. Dopamine

• Mechanism: Dose-dependent receptor stimulation

  • Low dose: D1 (renal vasodilation)

  • Moderate dose: β1 (inotropy)

  • High dose: α1 (vasoconstriction)

• Indication:

  • Historically used in hypotension with bradycardia

  • No longer preferred in septic shock due to arrhythmia risk

• Route: IV infusion

• Brand: Intropin® (discontinued in some countries)

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4. Dobutamine (Primarily an inotrope with vasopressor effect)

• Mechanism: β1 agonist > β2/α1 → increased cardiac output with mild vasodilation

• Indication:

  • Cardiogenic shock with low cardiac output and normotension

• Route: IV infusion

• Brand: Dobutrex®

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5. Phenylephrine

• Mechanism: Selective α1 agonist → peripheral vasoconstriction

• Indication:

  • Hypotension with tachyarrhythmia (e.g., AFib with RVR)

  • Neurogenic shock

• Route: IV bolus or infusion

• Brand: Neo-Synephrine®

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6. Vasopressin (Arginine Vasopressin)

• Mechanism: V1 receptor agonist → vasoconstriction independent of adrenergic receptors

• Indication:

  • Septic shock (second-line adjunct to norepinephrine)

  • Post-cardiotomy vasoplegia

  • Diabetes insipidus

• Route: IV infusion

• Brand: Pitressin®

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7. Terlipressin

• Mechanism: Long-acting synthetic analog of vasopressin

• Indication:

  • Hepatorenal syndrome (HRS)

  • Variceal bleeding in cirrhosis

• Route: IV bolus or infusion

• Brand: Terlivaz® (FDA-approved for HRS)

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8. Angiotensin II

• Mechanism: AT1 receptor agonist → potent vasoconstriction and aldosterone release

• Indication:

  • Septic or distributive shock resistant to conventional vasopressors

• Route: IV infusion

• Brand: Giapreza®

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Comparison of Pharmacologic Properties

Agent	α1	β1	β2	V1	Receptor Type	Primary Use
Norepinephrine	++++	++	+	–	Catecholamine	Septic shock (1st line)
Epinephrine	+++	+++	++	–	Catecholamine	Anaphylaxis, ACLS
Dopamine	++	++	+	–	Catecholamine	Hypotension with bradycardia
Dobutamine	±	++++	++	–	Catecholamine (inotrope)	Cardiogenic shock
Phenylephrine	++++	–	–	–	Selective α1 agonist	Neurogenic shock
Vasopressin	–	–	–	++++	V1 receptor agonist	Septic shock adjunct
Terlipressin	–	–	–	++++	V1 receptor analog	Hepatorenal syndrome
Angiotensin II	–	–	–	–	AT1 receptor agonist	Vasodilatory shock

Indications by Shock Type

Shock Type	Preferred Vasopressors
Septic Shock	Norepinephrine ± Vasopressin
Cardiogenic Shock	Dobutamine ± Norepinephrine
Neurogenic Shock	Phenylephrine or Norepinephrine
Anaphylactic Shock	Epinephrine (IM or IV)
Hypovolemic Shock	Fluids first → Vasopressors if unresponsive
Hepatorenal Syndrome	Terlipressin ± albumin
Refractory Distributive	Angiotensin II (Giapreza)

Contraindications

• Hypovolemia uncorrected: Vasopressors should not be started before fluid resuscitation

• Known hypersensitivity to the agent

• Dopamine: Avoid in patients with tachyarrhythmias or pheochromocytoma

• Dobutamine: Avoid in patients with obstructive cardiomyopathy

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Precautions and Monitoring

• Central line administration preferred due to risk of extravasation and tissue necrosis

• Invasive blood pressure monitoring (e.g., arterial line) in ICU settings

• Monitor:

  • Heart rate, rhythm (ECG)

  • Mean arterial pressure (MAP)

  • Urine output (renal perfusion)

  • Serum lactate (shock resolution marker)

  • Signs of peripheral ischemia (toes, fingers)

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Adverse Effects

• Arrhythmias (especially dopamine, epinephrine, dobutamine)

• Tachycardia, hypertension, reflex bradycardia (phenylephrine)

• Ischemia: Myocardial, mesenteric, digital

• Hyperglycemia: Epinephrine

• Hyponatremia: Vasopressin (antidiuretic effect)

• Tissue necrosis if extravasated (especially norepinephrine)

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Drug Interactions

• MAO inhibitors + Catecholamines: Risk of hypertensive crisis

• Beta-blockers: May blunt effects of epinephrine or dopamine

• Tricyclic antidepressants: Potentiate catecholamine response

• Digoxin + Dobutamine: Risk of arrhythmia

• Inhalational anesthetics: Sensitize myocardium to catecholamines

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Reversal Agents and Antidotes

• Phentolamine: Used to treat local vasopressor extravasation by α-blockade

• Nitroprusside or Labetalol: May be used in hypertensive crises due to overdose

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Clinical Guidelines and Recommendations

• Surviving Sepsis Campaign (SSC) recommends:

  • First-line: Norepinephrine

  • Add-on: Vasopressin (up to 0.03 units/min)

  • Consider epinephrine or angiotensin II if hypotension persists

• ACLS Guidelines:

  • Epinephrine 1 mg IV every 3–5 min in cardiac arrest

• ESC/ACC Guidelines for heart failure and shock recommend dobutamine for inotropy when hypotension is minimal