What are the classification, indications, route, dosage, contraindications, precautions, adverse reactions, interactions, and hemodynamic effects of norepinephrine?

Norepinephrine: Classification, Indications, Administration, and Effects

Norepinephrine is a catecholamine with high affinity for α-receptors that is primarily used to increase systemic vascular resistance in hypotensive states, particularly when blood pressure remains low despite adequate fluid resuscitation. 1, 2

Classification

• Vasopressor (specifically an inoconstrictor) with predominant α-adrenergic receptor activity 3
• Catecholamine that acts primarily on α-receptors to cause vasoconstriction 4
• Has moderate β1 effects but minimal β2 effects 5

Indications

• First-line vasopressor for severe hypotension (systolic BP ≤70 mmHg) with low peripheral vascular resistance 2, 4
• Preferred in situations with low blood pressure related to reduced systemic vascular resistance such as septic shock 1
• Recommended for initial management of post-cardiac arrest hypotension 4
• Used in cardiogenic shock when combination of inotropic agents and fluid challenge fails to restore adequate arterial and organ perfusion 1

Route and Dosage

• Administered intravenously, preferably through a central venous line to prevent tissue necrosis from extravasation 2, 6
• Typical dosage range: 0.2-1.0 μg/kg/min 1
• FDA-approved preparation: Add 4 mg/4 mL of norepinephrine to 1,000 mL of 5% dextrose solution (resulting in 4 mcg/mL) 6
• Initial dose: 2-3 mL/min (8-12 mcg/min) with adjustment based on blood pressure response 6
• Average maintenance dose: 0.5-1.0 mL/min (2-4 mcg/min) 6
• Titrate to achieve a target mean arterial pressure (MAP) of 65-100 mmHg 2, 4

Contraindications and Precautions

• Relatively contraindicated in hypovolemic patients; always correct volume depletion before or concurrently with norepinephrine administration 2, 6
• Use cautiously in patients with ischemic heart disease as it may increase myocardial oxygen requirements 2, 4
• In cardiogenic shock, use with caution and only transiently due to risk of increasing afterload and further decreasing end-organ blood flow 1
• Higher doses (>10 mcg/minute) are associated with increased mortality and should be avoided if possible 2

Adverse Reactions and Side Effects

• Increased myocardial oxygen consumption 2, 4
• Tissue necrosis if extravasation occurs 2, 6
• Arrhythmias at higher doses 2
• Excessive vasoconstriction leading to end-organ hypoperfusion 2, 4
• May reduce end-organ perfusion, particularly renal and mesenteric blood flow 1
• In septic shock, however, it may actually improve renal blood flow and urine output 2, 4

Interactions

• Concurrent use with phosphodiesterase inhibitors may cause severe hypotension 1
• May have additive effects when combined with other vasopressors 4
• Often combined with dobutamine to improve hemodynamics in cardiogenic shock 1

Assessments Before and After Administration

• Before administration:

  • Assess volume status; correct hypovolemia before or during administration 2, 6
  • Obtain baseline vital signs, particularly blood pressure 2
  • Ensure appropriate vascular access, preferably central venous 2, 7

• During/after administration:

  • Continuous hemodynamic monitoring is essential 2
  • Monitor for signs of extravasation; if it occurs, infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site 2, 4
  • Assess peripheral perfusion regularly (skin temperature, capillary refill) 2
  • Monitor urine output as a marker of adequate renal perfusion 4

Hemodynamic and Multi-system Effects

• Cardiovascular effects:

  • Increases systemic vascular resistance 1, 3
  • Increases mean arterial pressure 3, 8
  • Less increase in heart rate compared to epinephrine 1
  • May increase cardiac afterload, potentially reducing cardiac output in patients with heart failure 1

• Renal effects:

  • Typically causes renal vasoconstriction 4, 3
  • In septic shock, may improve renal blood flow and urine output despite vasoconstriction 2, 4

• Splanchnic effects:

  • Causes mesenteric vasoconstriction 4, 3
  • May reduce splanchnic blood flow 1

Evaluation and Desired Outcomes

• Primary desired outcome: Restoration and maintenance of adequate mean arterial pressure (target 65-100 mmHg) 2, 4
• Secondary outcomes:
  • Improved tissue perfusion (assessed by lactate clearance, urine output, mental status) 4
  • Reduced need for fluid administration 4
  • Weaning from vasopressor support 2

Important Clinical Considerations

• Norepinephrine should be weaned gradually (decrease by 25% of current dose every 30 minutes as tolerated) 2
• If blood pressure remains inadequate despite increasing doses, consider adding a second vasopressor agent 2, 8
• Recent evidence suggests peripheral administration may be safe with proper monitoring, potentially avoiding central line placement in some patients 7
• For refractory hypotension, consider escalating the dose or adding alternative vasopressors such as vasopressin 2, 8