What is the recommended dose and frequency of norepinephrine (noradrenaline) administration?

From the Guidelines

Norepinephrine should be administered as a continuous intravenous infusion at an initial dose of 0.1-0.5 mcg/kg/min, titrated every 3-5 minutes to achieve the desired blood pressure response, usually targeting a mean arterial pressure (MAP) of 65-70 mmHg, as recommended by the Surviving Sepsis Campaign guidelines 1. The maximum recommended dose is generally 2-3 mcg/kg/min, though higher doses may be used in refractory shock.

Key Considerations

• Norepinephrine should be administered through a central venous catheter whenever possible to minimize the risk of extravasation and tissue necrosis.
• The medication is prepared as a dilution, commonly 4-8 mg in 250 mL of D5W or normal saline, resulting in a concentration of 16-32 mcg/mL.
• Continuous hemodynamic monitoring is essential during administration, including blood pressure, heart rate, and urine output.

Mechanism of Action

Norepinephrine works primarily as a potent alpha-1 adrenergic receptor agonist causing peripheral vasoconstriction, with some beta-1 activity increasing cardiac contractility, making it particularly effective for vasodilatory shock states like septic shock where it helps restore vascular tone and improve tissue perfusion 1.

Clinical Guidelines

The Surviving Sepsis Campaign guidelines recommend norepinephrine as the first-choice vasopressor, with the option to add vasopressin or epinephrine to achieve the desired blood pressure response 1.

Administration and Monitoring

• Initial dose: 0.1-0.5 mcg/kg/min
• Titration: every 3-5 minutes
• Target MAP: 65-70 mmHg
• Maximum dose: 2-3 mcg/kg/min
• Administration route: central venous catheter
• Monitoring: continuous hemodynamic monitoring, including blood pressure, heart rate, and urine output.

From the Research

Norepinephrine Administration

• The recommended dose and frequency of norepinephrine administration can vary depending on the patient's condition and the severity of septic shock 2, 3.
• Early administration of norepinephrine is beneficial for septic shock patients to restore organ perfusion, with a recommended target mean arterial pressure of at least 65 mmHg 2.
• The choice of starting norepinephrine administration early should be adapted to the patient's condition, with consideration given to patients with profound hypotension or those at risk of fluid accumulation 3.

Dosing Considerations

• Weight-based dosing of norepinephrine may be necessary, particularly in obese patients, with studies suggesting that obese patients require lower weight-based doses of norepinephrine compared to non-obese patients 4, 5.
• However, the use of weight-based dosing does not necessarily lead to earlier achievement of goal mean arterial pressure in obese patients with septic shock 5.

Practice Patterns

• Practice patterns for the initiation of secondary vasopressors and adjunctive corticosteroids during septic shock can vary significantly between hospitals, with the hospital of admission being a strong predictor of the treatment strategy used 6.
• The norepinephrine dose at which secondary vasopressors and corticosteroids are initiated can also vary widely between hospitals, ranging from 6.4 μg/min to 92.6 μg/min for vasopressors and 3.0 μg/min to 32.7 μg/min for corticosteroids 6.