What are the dosages for a norepinephrine (Levophed) drip?

From the Guidelines

Norepinephrine drip dosing should start at 0.5 mg/h and be increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h, 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, as recommended by the most recent guidelines 1. When initiating norepinephrine therapy, it is essential to consider the patient's individual hemodynamic status and adjust the dose accordingly. The primary goal of norepinephrine administration is to restore adequate organ perfusion, which can be achieved by titrating the dose to achieve a mean arterial pressure (MAP) of 65 mmHg or higher.

• Key considerations for norepinephrine administration include:
  • Starting dose: 0.5 mg/h, which can be adjusted based on patient response and clinical guidelines 1
  • Dose titration: increase by 0.5 mg/h every 4 hours, as needed, to achieve the desired hemodynamic response
  • Maximum dose: 3 mg/h, although most patients respond to lower doses
  • Administration: continuous intravenous infusion, preferably through a central venous catheter, diluted in D5W or normal saline to a concentration of 4-16 mcg/mL
• Regular monitoring of blood pressure, heart rate, and tissue perfusion is crucial during norepinephrine administration to ensure optimal dosing and minimize potential adverse effects. Norepinephrine works primarily as an alpha-adrenergic agonist, causing vasoconstriction, which increases systemic vascular resistance and blood pressure, and also has some beta-1 adrenergic effects that support cardiac output. As the first-line vasopressor for most types of shock, particularly septic shock, norepinephrine effectively restores organ perfusion while having less impact on heart rate compared to other vasopressors, as supported by earlier guidelines 1. However, the most recent recommendation 1 should be prioritized in clinical practice, ensuring that patients receive evidence-based care that optimizes their outcomes in terms of morbidity, mortality, and quality of life.

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. Average Dosage: Add the content of the vial (4 mg/4 mL) of LEVOPHED to 1,000 mL of a 5 percent dextrose containing solution. Each mL of this dilution contains 4 mcg of the base of LEVOPHED Give this solution by intravenous infusion. After observing the response to an initial dose of 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow to establish and maintain a low normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic) sufficient to maintain the circulation to vital organs The average maintenance dose ranges from 0. 5 mL to 1 mL per minute (from 2 mcg to 4 mcg of base).

The dosages for a norepinephrine drip are as follows:

• Initial dose: 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute
• Average maintenance dose: 0.5 mL to 1 mL per minute (from 2 mcg to 4 mcg of base)
• High dosage: may be necessary in some cases, with daily doses as high as 68 mg base or 17 vials, but should be titrated according to the response of the patient 2

From the Research

Norepinephrine Drip Dosages

• The optimal dosage of norepinephrine for septic shock patients is not explicitly stated in the provided studies, but the goal is to target a mean arterial pressure (MAP) of at least 65 mmHg 3.
• Recent data suggest that early administration of norepinephrine is beneficial for septic shock patients to restore organ perfusion, and the MAP target should be individualized 3.
• When hypotension is refractory to norepinephrine, it is recommended to add vasopressin, which acts on other vascular receptors than α1-adrenergic receptors 3.
• The use of norepinephrine and vasopressin in hemorrhagic shock has been studied, and it has been found that norepinephrine increases MAP via its α-1-mediated vasoconstriction and its β1-related increase in cardiac output, while vasopressin induces vasoconstriction through activation of V1-a receptors 4.
• A study on septic shock patients found that differing MAP levels by norepinephrine infusion induced diverse peripheral perfusion index (PI) responses, and these PI responses may be independent of the change in cardiac output 5.

Key Considerations

• The dosage of norepinephrine should be titrated to achieve the desired MAP target, and the response of the patient should be closely monitored 3, 5.
• The addition of vasopressin may be necessary in cases of refractory hypotension, and the use of vasopressin and norepinephrine together has been studied in various shock states 3, 6, 4.
• The choice of vasopressor and the dosage used should be based on the individual patient's underlying pathophysiology of shock and the desired pharmacologic effects 7.