How is norepinephrine (noradrenaline) administered?

From the Guidelines

Norepinephrine should be administered intravenously through a central venous catheter as a continuous infusion, with a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h, as recommended by the most recent guidelines 1. The administration of norepinephrine is crucial in managing hypotension, particularly in septic shock, neurogenic shock, and other vasodilatory shock states. Key considerations for administration include:

• Starting dose: 0.5 mg/h, which can be increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h 1
• Administration route: intravenous through a central venous catheter as a continuous infusion
• Monitoring: continuous blood pressure monitoring is essential, preferably with an arterial line
• Titration: the dose should be titrated based on blood pressure response, with the goal of increasing the mean arterial pressure by ≥10 mm Hg and/or the urine output to >50 mL/h for at least 4 hours 1
• Precautions: norepinephrine should never be given as a bolus or through peripheral IVs due to risk of extravasation and tissue necrosis The primary mechanism of action of norepinephrine is as an alpha-adrenergic agonist, causing vasoconstriction, which increases systemic vascular resistance and blood pressure, with additional beta-1 effects that support cardiac output. Overall, the administration of norepinephrine requires careful consideration of the patient's hemodynamic status and close monitoring to ensure effective and safe use, as supported by the guidelines 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Norepinephrine Bitartrate Injection is a concentrated, potent drug which must be diluted in dextrose containing solutions prior to infusion. An infusion of LEVOPHED should be given into a large vein Give this solution by intravenous infusion. Insert a plastic intravenous catheter through a suitable bore needle well advanced centrally into the vein and securely fixed with adhesive tape, avoiding, if possible, a catheter tie-in technique as this promotes stasis An IV drip chamber or other suitable metering device is essential to permit an accurate estimation of the rate of flow in drops per minute

Administration of Norepinephrine:

• Norepinephrine should be administered by intravenous infusion into a large vein.
• The solution should be diluted in a dextrose containing solution prior to infusion.
• An IV drip chamber or other suitable metering device is necessary to accurately estimate the rate of flow.
• The infusion rate should be titrated according to the response of the patient to establish and maintain a low normal blood pressure 2.

From the Research

Administration of Norepinephrine

• Norepinephrine is typically administered as a first-line agent in septic shock to correct hypotension due to depressed vascular tone 3, 4.
• The optimal timing to start norepinephrine is early, as it can increase cardiac output, improve microcirculation, and avoid fluid overload 3.
• Norepinephrine can be administered through a peripheral intravenous catheter (PIV) at low doses for less than 24 hours using a protocol, which can help prevent unnecessary central line insertion and minimize the risk of central line complications 5.
• The dose of norepinephrine can be increased up to ≥1 µg/kg/min in cases of refractory hypotension, but it is often recommended to combine it with other vasopressors such as vasopressin to raise the mean arterial pressure (MAP) to target or to decrease the norepinephrine dosage 4.

Target Mean Arterial Pressure

• The target mean arterial pressure (MAP) is typically set at 65 mmHg, but it can be individualized based on factors such as history of chronic hypertension or value of central venous pressure (CVP) 3, 4.
• The diastolic arterial pressure (DAP) can be used as a marker of vascular tone to identify patients who need norepinephrine urgently 4.

Combination with Other Vasopressors

• Norepinephrine can be combined with other vasopressors such as vasopressin or epinephrine in cases of refractory hypotension, but the optimal adjuvant vasopressor remains controversial 4, 6.
• Studies have shown that the combination of norepinephrine and vasopressin or epinephrine can be effective in achieving the target MAP, but the choice of adjuvant vasopressor may depend on individual patient factors 6, 7.