From the Guidelines
The maximum administration rate of norepinephrine is 3 mg/hour.
Administration Details
- Norepinephrine is given as a continuous IV infusion, typically in an intensive care unit setting, starting at 0.5 mg/hour to achieve an increase in mean arterial pressure of at least 10 mm Hg or an increase in urine output of >200 mL/4 hours 1.
- If at least one of these goals is not achieved, the dose of norepinephrine is increased every 4 hours in increments of 0.5 mg/hour up to a maximum of 3 mg/hour 1.
Key Considerations
- The use of norepinephrine is relatively contraindicated in patients with hypovolemia, as it may increase myocardial oxygen requirements, mandating cautious use in patients with ischemic heart disease 1.
- Norepinephrine usually induces renal and mesenteric vasoconstriction, but in sepsis, it improves renal blood flow and urine output 1.
- Albumin is also given to maintain a central venous pressure between 4 and 10 mm Hg 1.
From the FDA Drug Label
DOSAGE & ADMINISTRATION ... 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 High Dosage: Great individual variation occurs in the dose required to attain and maintain an adequate blood pressure. In all cases, dosage of LEVOPHED should be titrated according to the response of the patient The maximum administration rate of norepinephrine is not explicitly stated in the drug label, but the initial dose is 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute, and the average maintenance dose ranges from 0.5 mL to 1 mL per minute (from 2 mcg to 4 mcg of base). However, it is mentioned that high dosage may be necessary, with daily doses as high as 68 mg base or 17 vials, but the exact maximum administration rate is not provided 2.
From the Research
Maximum Administration Rate of Norepinephrine
The maximum administration rate of norepinephrine is a critical aspect of its usage in clinical settings. According to the available evidence:
- A study published in 2015 3 found that the death rate reached 90% for patients receiving more than 1 μg/kg per minute of norepinephrine.
- Another study from 2016 4 reported a case where a patient received norepinephrine at a flow rate of 7-10 times the highest reported rate (3 μg/kg/min) without adverse effects.
- A 2013 study 5 found that the reason, dose, and duration of norepinephrine administration did not have prognostic significance, but scores greater than 40 on the Acute Physiology and Chronic Health Evaluation II, bicarbonate levels less than 9.0 mEq/L, or receipt of an epinephrine dose of 0.25 μg/kg per minute or greater were associated with 100% mortality.
- A 2024 survey 6 of critical care clinicians found wide variability in norepinephrine dosing practices, including maximum doses allowed, with a median protocolized maximum dose of 1 μg/kg/min for weight-based dosing.
- A 2020 retrospective study 7 found that a maximum norepinephrine dosage within 24 hours of ICU admission (MD24) of 0.6 μg/kg/min was significantly associated with 7-day mortality in patients with septic shock.
Key Findings
- The maximum administration rate of norepinephrine varies widely in clinical practice.
- High doses of norepinephrine (e.g., >1 μg/kg/min) may be associated with increased mortality.
- The use of weight-based dosing and protocolized maximum doses may help guide norepinephrine administration.
- Further research is needed to determine the optimal maximum administration rate of norepinephrine in different clinical contexts.