What are the mechanisms of action, dosages, and indications for pressors (vasopressors) in the Intensive Care Unit (ICU) for managing hypotension?

Vasopressors in the ICU: Mechanisms of Action, Dosages, and Indications

Norepinephrine is the first-choice vasopressor for managing hypotension in ICU patients with vasodilatory shock, typically starting at 0.01-0.5 μg/kg/min and titrating to maintain a MAP of 65 mmHg. 1, 2

Primary Vasopressors and Their Mechanisms

Norepinephrine

• Acts primarily on α1-adrenergic receptors causing vasoconstriction with some β1 activity (increasing cardiac contractility and heart rate) 3
• Initial dosage: 0.01-0.5 μg/kg/min IV continuous infusion 2
• First-line agent for septic shock and general vasodilatory shock 1, 3
• Increases systemic vascular resistance (SVR) with minimal effect on heart rate 3

Vasopressin

• Acts on V1 receptors causing vasoconstriction through a non-adrenergic mechanism 4
• Dosage: 0.01-0.07 units/min for septic shock; 0.03-0.1 units/min for post-cardiotomy shock 4
• Indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines 4
• Often used as a second-line agent in combination with norepinephrine 2
• Particularly useful in septic or liver patients with relative vasopressin deficiency 1

Phenylephrine

• Pure α1-adrenergic receptor agonist causing vasoconstriction without β effects 5
• Dosage: Bolus 50-250 mcg IV; continuous infusion 0.5-6 mcg/kg/min 5
• Used for perioperative hypotension (0.5-1.4 mcg/kg/min) and vasodilatory shock (0.5-6 mcg/kg/min) 5
• Useful when tachycardia needs to be avoided 3

Epinephrine

• Acts on both α and β receptors (α1: vasoconstriction; β1: increased contractility and heart rate; β2: bronchodilation) 3
• Typically added as second-line when additional agent is needed 1
• Can be used as push-dose (10-20 μg IV every 2 minutes) for acute hypotension management 6
• May cause tachycardia, arrhythmias, and increased lactate levels 3

MAP Targets and Individualization

• Standard target MAP is 65 mmHg for most ICU patients with shock 1, 2
• Below this threshold, autoregulation in critical vascular beds can be lost, making perfusion linearly dependent on pressure 1
• In patients with chronic hypertension, a higher MAP target (75-85 mmHg) may be beneficial to reduce acute kidney injury 2
• In elderly patients (>75 years), a lower MAP target (60-65 mmHg) may be appropriate 2

Special Considerations for Pulmonary Hypertension

• In pulmonary arterial hypertension (PAH), maintain systemic vascular resistance (SVR) greater than pulmonary vascular resistance (PVR) 1
• Inotropes with neutral or beneficial effects on PVR include dobutamine, milrinone, and epinephrine 1
• Dobutamine is often preferred over milrinone due to shorter half-life 1
• Consider adding vasopressin to offset potential drop in SVR, particularly in septic or liver PH patients 1

Peri-intubation Hypotension Management

• Peri-intubation hypotension is associated with increased ICU mortality 1
• Bolus doses of phenylephrine (50-200 μg) or ephedrine (5-25 mg) can be used 1
• Continuous infusions of norepinephrine, epinephrine, vasopressin, dopamine, or phenylephrine may be used as part of an intubation bundle 1
• Studies have shown improvement in blood pressure after vasopressor bolus administration during intubation 1

Practical Approach to Vasopressor Selection and Use

1. Initial Assessment

   • Determine type of shock (vasodilatory, cardiogenic, hypovolemic, obstructive) 3
   • Ensure adequate fluid resuscitation before or concurrent with vasopressor initiation 1
   • Establish appropriate MAP target (typically 65 mmHg) 2

2. First-line Therapy

   • Start norepinephrine at 0.01-0.5 μg/kg/min for vasodilatory shock 2, 3
   • Titrate to achieve target MAP while monitoring for adverse effects 3

3. Second-line Options

   • Add vasopressin (up to 0.03 U/min) if norepinephrine dose is escalating 2
   • Consider epinephrine if additional agent is needed 1
   • Add dobutamine if cardiac output is inadequate despite adequate filling pressures 3

4. Monitoring and Adjustment

   • Assess response using dynamic (pulse pressure variation, stroke volume variation) or static variables (arterial pressure, heart rate) 1
   • Monitor for tissue perfusion using lactate levels, urine output, mental status, and skin perfusion 2
   • Wean vasopressors as patient condition improves, continuing fluid resuscitation 1

Common Pitfalls and Complications

• Excessive vasoconstriction causing organ ischemia/infarction 3
• Hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias 3
• Medication errors with push-dose vasopressors (incorrect dosing or inappropriate use) 1
• Relying solely on MAP without assessing other indicators of tissue perfusion 2
• Targeting excessively high MAP (85 mmHg) can increase risk of arrhythmias 2

Emerging Trends

• Most ICUs (70.6%) do not have specific hypotension treatment protocols, though the majority would like to have one 7
• Statistical models using BP trend features may predict hypotension episodes before onset 8
• New strategies may include starting multiple vasopressors with complementary mechanisms of action 3
• Personalized vasopressor selection based on predictive biomarkers is an emerging concept 3