What are the indications, dosages, complications, and mechanism of action of noradrenaline (norepinephrine) in treating hypotension?

Noradrenaline (Norepinephrine): Indications, Dosages, Complications, and Mechanism of Action

Norepinephrine is the first-line vasopressor for treating severe acute hypotension, with an initial dose of 0.25-0.375 mL/min (8-12 mcg/min) titrated to maintain a mean arterial pressure of 65 mmHg. 1

Mechanism of Action

• Norepinephrine acts primarily on alpha-adrenergic receptors to cause vasoconstriction, increasing systemic vascular resistance and mean arterial pressure 2
• It also has beta-adrenergic effects that provide mild inotropic support, increasing cardiac output through improved cardiac preload and contractility 3
• The drug increases venous tone, particularly in the splanchnic circulation, which actively shifts blood volume to the systemic circulation 4

Indications

• Restoration of blood pressure in adult patients with acute hypotensive states 1
• First-line vasopressor for septic shock after adequate fluid resuscitation 4, 2
• Treatment of persistent hypotension despite fluid therapy in trauma resuscitation 4
• Management of cardiogenic shock and post-cardiac arrest hypotension 2

Dosage and Administration

• Initial dose: 0.25-0.375 mL/min (8-12 mcg/min) 1
• Average maintenance dose: 0.0625-0.125 mL/min (2-4 mcg/min) 1
• Alternative dosing: 0.1-0.5 mcg/kg/min, titrated to effect 4, 2
• Target mean arterial pressure (MAP) of 65 mmHg, though this should be higher (75-85 mmHg) in patients with chronic hypertension 4, 2, 5
• Should be administered through a central venous line whenever possible to prevent tissue necrosis from extravasation 2

Complications and Adverse Effects

• Tissue ischemia and necrosis from extravasation, requiring immediate infiltration with 10-15 mL of saline containing 5-10 mg of an adrenergic blocking agent (phentolamine) 1
• Rebound hypotension after abrupt discontinuation - requires gradual tapering 1
• Cardiac arrhythmias, particularly in patients with underlying heart disease 1
• Excessive vasoconstriction leading to organ ischemia, particularly at higher doses (≥0.6 μg/kg/min) 6
• Increased myocardial oxygen requirements, requiring cautious use in patients with ischemic heart disease 2
• Allergic reactions due to sodium metabisulfite content 1
• Potential for decreased organ perfusion at excessive doses, with higher SOFA scores at 24 hours associated with doses ≥0.6 μg/kg/min 6

Clinical Considerations

• Early administration of norepinephrine is beneficial in septic shock to restore organ perfusion and avoid fluid overload 7
• Fluid resuscitation should be initiated before or simultaneously with norepinephrine in hypovolemic states 4, 5
• In refractory hypotension, vasopressin (up to 0.03 U/min) can be added to norepinephrine to increase MAP or reduce norepinephrine dosage 2, 5
• Epinephrine (0.1-0.5 mcg/kg/min) is an alternative when additional support is needed 2
• Continuous monitoring of ECG, blood pressure, oxygen saturation, and urine output is necessary during administration 5
• Avoid fluid overload in patients with generalized peritonitis as it may aggravate gut edema and increase intra-abdominal pressure 4

Special Populations

• In traumatic hemorrhagic shock, high-dose norepinephrine (≥0.6 μg/kg/min) has been associated with increased organ dysfunction and should be used cautiously 6
• Norepinephrine has shown efficacy in neonatal septic shock (0.5 ± 0.4 μg/kg/min), improving blood pressure, urine output, and decreasing lactate levels 8
• Elderly patients may be at greater risk of developing adverse reactions and may require lower doses 1